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Table of Contents

Program-ata-Glance

2–5

General Information

11 – 12

Scientific Program

14 – 20

Poster Information

21 – 22

Exhibitor Directory

50 - 57

1. 2 – 5. 6. 7. 8. 9 – 10. 11 – 12. 13. 14 – 20. 21 – 22. 23 – 41. 42 – 44. 45. 46. 47 – 49. 50 – 57. 58.

Welcome Letter from Meeting Chairman, Denis Grant Program-at-a-Glance 10th International ISSX Meeting Committees Future ISSX Meetings ISSX Leadership & Staff Society Awards General Information Westin Harbour Castle Maps Scientific Program Poster Information Poster Details Industry-Sponsored Symposia Corporate Sponsors ISSX Party at the Hockey Hall of Fame Special Advertising Section Exhibitor Directory Metropolitan Ballroom Exhibit Hall Floor Plan


Dear Colleagues and Guests, On behalf of the Meeting Organizing Committee, the Scientific Advisory Board and ISSX Council, it is my great pleasure to welcome you to the 10 th International ISSX Meeting in Toronto! I hope you'll agree that we've managed to assemble an outstanding scientific program that includes state-of-the-art Short Courses, a thought-provoking Keynote Lecture, and Plenary Sessions, Parallel Sessions, Industry-Sponsored Symposia and Poster Sessions on a broad range of exciting and timely topics from leading academic and industry scientists in the field of xenobiotic disposition, response and toxicity. We're also thrilled to have the enthusiastic and active participation of a large number of industrial sponsors who will be more than happy to provide you with access to information on the latest laboratory advances and technologies to support your research. I hope that you will take every advantage of this opportunity to hear, meet and discuss your science with your colleagues and friends both during and outside of the formal meeting proceedings during your stay. I would also like to extend to you my most heartfelt welcome to the City of Toronto, capital of the Province of Ontario, Canada's largest city and its cultural, entertainment and financial core. Sitting at the point where the Humber and Don Rivers flow into Lake Ontario, Toronto (from the Iroquois word for "place where trees stand in the water") is a vibrant, safe and strongly multicultural metropolis of over 2.5 million inhabitants, but it is also known locally as both "The City of Neighbourhoods" (there are 140 of them in all!) and "The City Within a Park" due to its extensive network of parks, ravine green spaces and lakeside waterfront. This means that a short walk or transit trip within the city can take you from a lively and densely populated downtown core through areas that may feel like small-town communities or even country wilderness. I encourage you to enjoy all of the natural, cultural, culinary and entertainment options available to you during your time with us. Sincerely,

Denis Grant Chair, Meeting Organizing Committee 1


Program-at-a-Glance Sunday, September 29, 2013 07:30 – 19:00 | Metropolitan Ballroom Foyer Registration Open 08:00 – 09:00 | Harbour Ballroom Foyer Short Course I and II Attendee Continental Breakfast 09:00 – 12:00 | Harbour Ballroom C 09:00 – 12:00 | Harbour Ballroom AB Short Course I: Metabolomic Profiling as a Short Course II: Model Systems and Methods Tool for Identifying Novel Drug-Target for Assessing Uptake and Efflux of Small Interactions Molecules Chair: David Wishart, University of Alberta, Edmonton, AB, Canada

Chair: Reina Bendayan, University of Toronto, Toronto, ON, Canada

10:20 – 10:40 | Harbour Ballroom Foyer Refreshment Break for Short Course I Attendees 12:00 – 13:30 | Harbour Ballroom Foyer Short Course III and IV Attendee Box Lunch 13:30 – 16:30 | Harbour Ballroom AB Short Course III: Strategies and Techniques for Predicting Human Drug Metabolism and Drug-Drug Interactions

10:30 – 10:50 | Harbour Ballroom Foyer Refreshment Break for Short Course II Attendees

Chairs: Uwe Fuhr, Uniklinik Koln, Koln, Germany; Olavi Pelkonen, University of Oulu, Oulu, Finland

Chair: Ragu Ramanathan, QPS, Newark, DE, USA

13:30 – 16:30 | Harbour Ballroom C Short Course IV: Application of Novel Mass Spectrometric Methods to Drug Metabolism and Pharmacokinetics Studies

14:50 – 15:10 | Harbour Ballroom Foyer Refreshment Break for Short Course III and IV Attendees 18:15 – 18:45 | Frontenac Opening Welcome Address and Cultural Presentation Denis Grant, 10th International ISSX Meeting Chair and Bill Smith, ISSX President

18:45 – 19:30 | Frontenac Keynote Lecture: S1. Systems Pharmacology – Systems Biology Meets Drug Discovery & Development Douglas Lauffenburger, Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA, USA

19:30 – 21:30 | Metropolitan Ballroom Opening Welcome Reception with Exhibitors

Monday, September 30, 2013 07:30 – 18:00 | Metropolitan Ballroom Foyer Registration Open 07:45 – 08:45 | Pier 4/5

07:45 – 08:45 | Harbour Ballroom

Industry-Sponsored Symposium Promega Corporation

Industry-Sponsored Symposium Thermo Scientific

USING MULTI-PARAMETRIC OPTICAL ASSAYS WITH SPECIALIZED CELL-TYPES TO ENHANCE THE BIOLOGICAL RELEVANCE OF EARLY ADMET SCREENING

APPLICATIONS OF HRAM AND NEW TOOLS FOR METABOLITE IDENTIFICATION

09:00 – 10:30 | Frontenac Plenary Session 1: Drug-Metabolizing Enzymes as Potential Therapeutic Targets Chair: Paul Hollenberg, University of Michigan, Department of Pharmacy, Ann Arbor, MI, USA 2


Program-at-a-Glance 10:30 – 11:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters 11:00 – 12:00 | Frontenac 2013 International ISSX Awards Session Presented by John O. Miners, Chair, ISSX Awards Committee and ISSX President0-Elect/Secretary 2013 R.T. Williams Distinguished Scientific Achievement Award Presentation and Lecture Yuichi Sugiyama, Ph.D. 2013 Frederick J. Di Carlo Distinguished Service Award Presentation to Robert P. Hanzlik, Ph.D.

12:00 – 13:30 | Metropolitan Ballroom Lunch on Own, Poster Presentations, Visit Exhibitors 12:15 – 13:00 | Metropolitan Ballroom Foyer Graduate/Predoctoral Poster Awards Finalist Presentations A1 – A6 12:30 – 13:30 | Metropolitan Ballroom Poster Presentations P1 – P157: Absorption to Drug Discovery and Development

13:30 – 15:30 | Frontenac Parallel Session 1: Nuclear Receptors as Regulators of Drug Metabolism and as Therapeutic Targets

13:30 – 15:30 | Harbour Ballroom Parallel Session 2: Pharmacogenomics and Personalized Medicine: Progress in Clinical Implementation

Co-Chairs: Ulrich Zanger, Dr. Margarete FischerBosch Institute of Clinical Pharmacology, Stuttgart, Germany; Hongbing Wang, University of Maryland, School of Pharmacy, Department of Pharmaceutical Science, Baltimore, MD, USA

Chair: Rachel Tyndale, University of Toronto, Toronto, ON, Canada

15:30 – 16:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters 16:00 – 18:00 | Frontenac 16:00 – 18:00 | Harbour Ballroom Parallel Session 3: Regulation of Drug Parallel Session 4: Application of Structural Transporter Expression and Function Biology to the Prediction of Drug Response, Chair: Micheline Piquette-Miller, University of Metabolism and Toxicity Toronto, Toronto, ON, Canada

Chair: James Halpert, University of California, San Diego, CA, USA

18:00 | Pier 8/9 Student and New Investigator Reception

19:00 | Regatta ISSX President’s Reception

Registered students and postdoctoral attendees are invited to attend this reception.

By invitation.

Tuesday, October 1, 2013 07:30 – 14:30 | Metropolitan Ballroom Foyer Registration Open 07:45 – 08:45 | Harbour Ballroom

07:45 – 08:45 | Pier 4/5

Industry-Sponsored Symposium Bruker Daltonics

Industry-Sponsored Symposium Corning Incorporated

MALDI IMAGING MASS SPECTROMETRY: BRIDGING BIOLOGY AND CHEMISTRY TO ADVANCE DRUG DEVELOPMENT

USING CELL-BASED AND RECOMBINANT MODELS IN DRUG TRANSPORT

09:00 – 10:30 | Frontenac Plenary Session 2: Utility of Genetic and Epigenetic Technologies in Drug Development and Safety Assessment Chair: Ann Daly, Newcastle University, Institute of Cellular Medicine, Newcastle Upon Tyne, UK 3


Program-at-a-Glance 10:30 – 11:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters 11:00 – 13:00 | Frontenac 11:00 – 13:00 | Harbour Ballroom Parallel Session 5: Metabolism, Parallel Session 6: Cell Type Specific Pharmacokinetics and Interactions of Mechanisms of Adverse Drug Reactions Traditional Medicines and Natural Products Chair: Michael Aleo, Pfizer, Global Research and Co-Chairs: Chuan Li, Shanghai Institute of Materia Medica, Shanghai, China; Ge Lin, Chinese University Hong Kong, School of Biomedical Sciences, Hong Kong, China

Development, Groton, CT, USA

13:00 – 14:00 | Metropolitan Ballroom Lunch on Own, Poster Presentations, Visit Exhibitors 13:00 – 13:45 | Metropolitan Ballroom Foyer Postdoctoral Poster Awards Finalist Presentations A7 – A12 13:00 – 14:00 | Metropolitan Ballroom Poster Presentations P158 – P296: Drug Interaction to Metabolic Profiling

14:00 | Free Afternooon in Toronto

Wednesday, October 2, 2013 07:30 – 16:00 | Metropolitan Ballroom Foyer Registration Open 07:45 – 08:45 | Harbour Ballrom

07:45 – 08:45 | Pier 4/5

Industry-Sponsored Symposium Hepregen Corporation

Industry-Sponsored Symposium Bioreclamation IVT (formerly Celsis In Vitro Technologies)

USE OF HepatoPac™ - AN IMPROVED IN VITRO MODEL FOR METABOLITE IDENTIFICATION AND COMPOUND STABILITY

PREDICTIONS OF IN VIVO HETEROTROPIC ACTIVATION OF CYTOCHROME P450 ENZYMATIC ACTIVITY FROM IN VITRO SYSTEMS

09:00 – 10:30 | Frontenac Plenary Session 3: Identification and Use of Novel Biomarkers for Xenobiotic-Induced Toxicity Chair: David Riddick, University of Toronto, Toronto, ON, Canada

10:30 – 11:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters 11:00 – 13:00 | Frontenac 11:00 – 13:00 | Harbour Ballroom Parallel Session 7: Targeted Drug Delivery Parallel Session 8: Use of PB-PK Modeling in for Enhanced Therapy Pharmaceutical Safety Assessment Chair: Christine Allen, University of Toronto, Toronto, ON, Canada

Chair: Aleksandra Galetin, University of Manchester, Manchester, UK

13:00 – 14:30 | Metropolitan Ballroom Lunch on Own, Poster Presentations, Visit Exhibitors 13:00 – 14:00 | Metropolitan Ballroom Poster Presentations P297 – P470: Metabolism to Transporters

14:30 – 16:30 | Frontenac Parallel Session 9: Regulatory Perspectives in Drug-Drug Interactions and Metabolites in Safety Testing Chair: Greg Slatter, Amgen, Inc., Seattle, WA, USA

14:30 – 16:30 | Harbour Ballroom Parallel Session 10: Toxicogenomic and Metabolomic Profiling: Current Status and Future Utility in Assessing Drug Efficacy and Safety Chair: Tim Zacharewski, Michigan State University, East Lansing, MI, USA 4


Program-at-a-Glance 16:30 – 17:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters 19:00 – 22:00 | ISSX Party at the Hockey Hall of Fame (Ticketed Event) Bring your ticket and meet in the hotel lobby at 18:45 to walk over to the Hockey Hall of Fame.

Thursday, October 3, 2013 08:00 – 14:00 | Metropolitan Ballroom Foyer Registration Open 08:00 – 08:30 | Metropolitan Ballroom Foyer Morning Coffee Service Sponsored by 11th International ISSX Meeting in Busan, Korea 08:30 – 09:00 | Metropolitan Ballroom Foyer General Session: Introduction of the 11th International ISSX Meeting in Busan, Korea Meeting Organizing Committee Chairman, Jae-Gook Shin, Professor of Pharmacology/Clinical Pharmacology, Inje University, Busan, Korea

09:00 – 10:30 | Frontenac Plenary Session 4: Genetically Modified Animal Models for Predicting Human Drug Disposition and Response Chair: Xinxin Ding, Wadsworth Center, New York State Department of Health, Albany, NY, USA

10:30 – 10:45 | Frontenac 2013 International Meeting Poster Awards Presentation Presented by Denis Grant, 10th International ISSX Meeting Chair

10:45 – 11:00 | Frontenac Foyer Refreshment Break 11:00 – 13:00 | Frontenac Parallel Session 11: Tissue Imaging and Distribution Studies in Drug Development Chair: Yasuyoshi Watanabe, RIKEN Center for Life Science Technologies, Kobe, Japan

11:00 – 13:00 | Harbour Ballroom Parallel Session 12: Development and Uses of Hepatocyte-Derived and Hepatocyte-Like Cells for Predicting Human Drug Metabolism Chair: Martine Daujat-Chavanieu, INSERM, Montpellier, France

13:00 | Frontenac Closing Remarks Denis Grant, 10th International ISSX Meeting Chair and Bill Smith, ISSX President

October 3 – October 17, 2013 th

10 International ISSX Meeting Evaluation | www.issx.org/International2013/eval Submit your meeting evaluation by Friday, October 17 for a chance to win a free meeting registration to an ISSX meeting in 2014.

May 9 – 12, 2014 th

5 Asia Pacific ISSX Meeting | Tianjin, China www.issx.org/AP2014

October 19 – 23, 2014 19th North American ISSX Meeting / 29th JSSX Meeting | San Francisco, California, USA www.issx.org/NA2014

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10th International ISSX Meeting Committees Meeting Organizing Committee (MOC)

International Scientific Advisory Board

Meeting Chair

Ann Daly, Newcastle University, UK Patrick Dansette, UniversitĂŠ Paris Descartes, France Xinxin Ding, Wadsworth Center, USA Uwe Fuhr, University Hospital of Cologne, Germany Ron Hines, Medical College of Wisconsin, USA Paul Hollenberg, University of Michigan Medical School, USA Richard Kim, University of Western Ontario, Canada Steve Leeder, Children's Mercy Hospital, USA Chuan Li, Shanghai Institute of Materia Medica, China Peter Mackenzie, Flinders University School of Medicine, Australia Larry Marnett, Vanderbilt University School of Medicine, USA Urs Meyer (Past ISSX President), Biozentrum, University of Basel, Switzerland Deborah Nicoll-Griffith, Merck & Co., USA Franz Oesch, University of Mainz Institute of Toxicology, Germany B. Kevin Park, University of Liverpool, UK Olavi Pelkonen, University of Oulu, Finland Rory Remmel, University of Minnesota, USA A. David Rodrigues, Bristol-Myers Squibb, USA Glenn Sipes, University of Arizona College of Medicine, USA Bill Smith (ISSX President), Pfizer Inc. La Jolla Labs, USA Steven R. Tannenbaum, MIT, USA Ken Thummel, University of Washington, USA Jacques Turgeon, Centre Hospitalier de L'Universite de Montreal, Canada Donald J. Tweedie, Boehringer Ingelheim, USA Jack Uetrecht, University of Toronto, Canada Yasushi Yamazoe, Tohoku University, Japan Uli Zanger, Dr. Margarete Fischer-Bosch Institute, Germany

Denis M. Grant University of Toronto, Toronto, Ontario, Canada

Members Stelvio Bandiera University of British Columbia, Vancouver, British Columbia, Canada Jack Bend University of Western Ontario, London, Ontario, Canada Chantal Guillemette Laval University, Quebec City, Quebec, Canada Malle Jurima-Romet Celerion, Montreal, Quebec, Canada David K.H. Lee InterVivo Solutions, Inc., Mississauga, Ontario, Canada Tom Massey Queen’s University, Kingston, Ontario, Canada Eddie Morgan Emory University, Atlanta, Georgia, USA Sandy Pang University of Toronto, Toronto, Ontario, Canada Allan Rettie (SAC Member) University of Washington, Seattle, Washington, USA David Riddick University of Toronto, Toronto, Ontario, Canada Nathalie Rioux Epizyme, Cambridge, Massachusetts, USA Rachel Tyndale University of Toronto, Toronto, Ontario, Canada Peter Wells University of Toronto, Toronto, Ontario, Canada

Abstract Review and Poster Awards Committee Stelvio Bandiera Jack Bend Denis Grant Chantal Guillemette Malle Jurima-Romet David K.H. Lee Tom Massey

Eddie Morgan Sandy Pang Allan Rettie David Riddick Nathalie Rioux Rachel Tyndale Peter Wells

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Future ISSX Meetings Save the Dates and Make Plans to Present Your Work and Attend Our Upcoming Meetings 5th Asia Pacific ISSX Meeting May 9 - 12, 2014 Tianjin, China Meeting Chairs: Zhuohan Hu, Research Institute for Liver Diseases, and John Miners, Flinders University School of Medicine

19th North American ISSX Meeting / 29th JSSX Meeting Hilton San Francisco San Francisco, California, USA October 19 - 23, 2014 Meeting Chairs: Tetsuya Terasaki, Tohoku University, and Eric Johnson, Scripps Research Institute

20th North American Meeting Hilton Orlando Bonnet Creek Orlando, Florida, USA October 18 - 22, 2015 Meeting Chairs: Hartmut Derendorf, University of Florida, and Stephan Schmidt, University of Florida

11th International ISSX Meeting Busan Exhibition and Convention Center Busan, Korea June 12 - 16, 2016 Meeting Chair: Jae-Gook Shin, Inje University

ISSX organizes its scientific meetings on a regular schedule with an International Meeting held in one of the three major regions of the world every third year. Other meetings are held regionally in the intervening years, usually annually in North America, biennially in Europe, and in other parts of the world when possible and as appropriate. The Scientific Affairs Committee of ISSX is charged with the responsibility for setting the meetings calendar on behalf of the Society. An International ISSX Meeting is a meeting for the entire Society with a broad ranging program to serve the interests of all its various scientific and geographical constituencies. Meetings held in intervening years are organized to serve the interests of members regionally; they may be more specialized, and the majority of the invited speakers are generally from the region in which the meeting is held. Workshops on specific topics may also be held from time to time, and these will operate under the same general principles as the larger meetings of the society. We encourage our members to propose to organize an ISSX meeting. Individuals interested in organizing an ISSX meeting should follow the guidelines established for doing so. The document entitled "Guidelines for the Organization of ISSX Meetings" may be downloaded from the ISSX web site. Sample meeting proposals and other helpful information is posted there as well.

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ISSX Leadership & Staff ISSX Council Bill Smith, President John Miners, President-Elect/Secretary Charles Crespi, Treasurer Andrew Parkinson, Treasurer-Elect Thomas Baillie Ann Daly Brian Houston Richard Kim Paul Ortiz de Montellano Allan Rettie (SAC Chair, Ex-Officio) Ikumi Tamai Hiroshi Yamazaki

Nominations Committee Urs A. Meyer, Chair Jack Bend Liz Gillam Edmund Maser B. Kevin Park Hiroshi Suzuki Joan Zuo

Publications Committee Chandra Prakash, Chair Jo Cato, Newsletter Editor Jack Hinson, DMR Editor Gerry Kenna Patrick Murphy, Web Advisor Bill Smith, Council Liaison Henry Strobel Tsuyoshi Yokoi Kouichi Yoshinari

Awards Committee John Miners, Chair Tommy B. Andersson Phil Board Ann Daly Chantal Guillemette Paul Hollenberg Ikumi Tamai Geoff Tucker

Scientific Affairs Committee Allan Rettie, Chair Sonia de Morais Aleksandra Galetin Zhuohan Hu Margareta Hummarlund-Udenaes Heyo Kroemer Hiroyuki Kusuhara John Miners, ISSX President-Elect/Secretary Dean Naisbitt Scott Obach Mikihisa Takano Tetsuya Terasaki Rachel Tyndale Paolo Vicini

Finance Committee Eric Johnson, Chair Charles Crespi, ISSX Treasurer Min Huang Teruko Imai Laurence Kaminsky Andrew Parkinson, ISSX Treasurer-Elect Amin Rostami-Hodjegan Bill Smith, ISSX President Michael Voice

Membership Affairs Committee Hugues Dolgos, Chair Christine Beedham Ziqiang Cheng Natilie Hosea John Miners, Council Liaison David Stresser Ping Zhao

ISSX Staff Steven Kemp, CAE, Executive Director ZoĂŤ Fuller, Senior Program Coordinator Sarah Langan, Senior Program Associate Alexandra Zapple, Senior Coordinator, Event Services Brittany Jackson, Senior Associate, Event Services Sarah Duncan, Associate, Education and Learning Services April Jones, Senior Associate, IT Services Anam Mufti, Staff Accountant Russell Nuzum, Director, Financial Management and Accounting

Committee on Regulatory Affairs J. Greg Slatter, Chair Eva Gil Berglund Charlene McQueen Izumi Takashi Qing-li Wang Lei Zhang

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Society Awards The R.T. Williams Distinguished Scientific Achievement Award Sponsored by Charles Crespi and Family The 2013 R.T. Williams Distinguished Scientific Achievement Award is presented to an ISSX member or non-member from any region that has made substantial and seminal scientific contributions to the field over a sustained period. The focus of this award is the individual's scientific accomplishments and it is intended to recognize the best in the field internationally. The 2013 recipient is Yuichi Sugiyama, Ph.D., RIKEN Innovation Center, Research Cluster for Innovation, Saitama, Japan. Professor Sugiyama is a world leader in drug transporters and physiologicallybased pharmacokinetics. His work is firmly based on quantitative principles whereby drugs are absorbed, reach their target tissue (to produce their pharmacological effect), are metabolized, and eventually excreted. A central goal of his research is to establish reliable predictions of drug action in vivo, thereby optimizing drug therapy. By integrating physiological, molecular, and genetic studies with pharmacokinetics, Professor Sugiyama has created a new research area Molecular Pharmacokinetics. A physiologically-based molecular pharmacokinetic model takes into consideration all relevant processes in the body. Professor Sugiyama dissects these processes by creatively interweaving a range of approaches that include mathematical modeling, pathophysiology, enzyme kinetics, genetics, and the molecular biology of receptors, enzymes and transporters. His work has succeeded to a degree unmatched by any other laboratory. Of particular note is Professor Sugiyama’s leadership in the field of drug transporters - he has published many seminal papers in this area. Detailed in vitro studies with transporters now allow prediction of transporter-mediated drugdrug interaction in vivo, while genetic variations in transporter genes are being identified in his laboratory that can account for inter-individual differences in drug disposition and response. Overall, Professor Sugiyama has produced a remarkable body of scientific work, with a profound impact on how we understand the pharmacokinetics, pharmacodynamics and use of drugs. Professor Sugiyama was ranked by ISI as the most highly cited scientist in Pharmacology and Toxicology over the period 1997-2007. Professor Sugiyama has been actively involved in professional organizations for decades. Notably, he served as a Councilor of ISSX from 1998 – 2003 and was elected President-Elect in 2004. He then served as president of ISSX from 2006-2007 while concurrently serving as the President of JSSX. He was Chair of the Pharmaceutical Sciences World Conference in Kyoto in 2004, and has served as co-chair of a multitude of highly regarded international symposia over the years. To recognize and celebrate Professor Sugiyama’s substantial and sustained scientific contributions to the field of xenobiotic disposition spanning almost four decades, he is awarded the 2013 R.T. Williams Distinguished Scientific Achievement Award. Award Presentation and Lecture: Monday, September 30 | 11:00 – 12:00 | FRONTENAC

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Society Awards The Frederick J. Di Carlo Distinguished Service Award The 2013 Frederick J. Di Carlo Distinguished Service Award is presented to an ISSX member from any region with an illustrious record of important service to the Society and its goals. The 2013 recipient is Robert P. Hanzlik, Ph.D. Professor Hanzlik has a history of service to ISSX and its goals. A charter member of the Society, Professor Hanzlik helped establish what has become the premier association for academic and industrial researchers in this area. In the early years he worked diligently to advance ISSX by serving in leadership and service roles including Councilor (1984-1987) and as the first chairman of the Scientific Affairs Committee (1986-1987). He was active in organizing meetings, serving as the program co-chairman for the very first ISSX North American Symposium (1985) and organizing and presenting a short course titled “Reactive Metabolite Chemistry for Toxicologists” at the 2nd North American ISSX Meeting in Florida, organized by Fred Di Carlo and Richard Welch (1987). During the early 1990’s as ISSX grew, Professor Hanzlik’s steady hand and attention to detail significantly contributed to both the ISSX Bylaws Committee (1991) and the Publications Committee (1991-1995). Professor Hanzlik has also organized several successful symposia and short courses for ISSX (6th North American ISSX Meeting in North Carolina in 1994) and Program Committee member for the 4th International ISSX Meeting in Seattle (1995). Professor Hanzlik then accepted the highest levels of ISSX leadership and responsibility as ISSX president-elect (1994 and 1995), president (1996-1997) and past president (1998 -1999), providing a well-organized and strong leadership vision. In addition to his record of outstanding support and leadership to ISSX, Professor Hanzlik brings honor to ISSX as a distinguished scientist with an international reputation and as a leading trainer of more than 50 graduate students and post-doctoral fellows who now occupy positions in the pharmaceutical industry, non-profit organizations, and academia. He has published in excess of 150 scientific papers and has served as a member of editorial and advisory boards for several prestigious scientific journals. For his involvement, leadership, expertise, contributions, and commitment, ISSX is proud to honor Professor Robert P. Hanzlik with the 2013 Frederick J. Di Carlo Distinguished Service Award. Award Presentation: Monday, September 30 | 11:00 – 12:00 | FRONTENAC ASIA PACIFIC ISSX MEETING AWARDS www.issx.org/awards/nominations Nominations are now being accepted for the following awards to be presented at the 5th Asia Pacific ISSX Meeting in May, 2014. The two awards to be presented at this meeting are: Asia Pacific Scientific Achievement Award - Presented to an ISSX member who has made major scientific contributions to the field in the Asia Pacific region. The purpose of this award is to recognize meritorious contributions by senior or mid-career scientists that have had a major impact on research in the field. The award will consist of a plaque or medal, an honorarium, and travel support to the 5th Asia Pacific Meeting in Tianjin, China where a lecture will be presented by the awardee. Regional New Investigator Award - Presented to an ISSX member who has made significant contributions to the field during their early career years (normally within 5 -10 years from the time of receiving his/her highest earned degree). The purpose of this award is to encourage and recognize developing scientists who are active in the field within the Asia Pacific region. The award will consist of a plaque or medal, an honorarium, and travel support to the 5th Asia Pacific ISSX Meeting in Tianjin, China.

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General Information Meeting Location The Westin Harbour Castle, Toronto 1 Harbour Square Toronto, M5J 1A6, Canada (416) 869-1600 westinharbourcastletoronto.com

Abstract Publication Accepted abstracts are published in a special online issue of Drug Metabolism Reviews and on the ISSX Web site at www.issx.org/onlineabstracts.

Exhibitor Check-Off Card ISSX meeting attendees each have an Exhibitor Check-Off Card. Attendees who visit with exhibitors and get a minimum of 20 exhibiting company blocks initialed by a corresponding exhibitor representative will be eligible for one of four great prizes: x Complimentary Meeting Registration to the 19th North American ISSX Meeting/29th JSSX Meeting at the Hilton San Francisco in October 2014 x Four nights lodging (including room & tax) at the Hilton San Francisco Hotel during our meeting dates x Free membership in ISSX for 2014 x $100 Visa Gift Card Visit our exhibiting companies and ask an exhibitor staff member to initial your check-off card. Only check-off cards with valid exhibitor initials in a minimum of 20 booth space blocks will be considered to be complete and thereby eligible to be entered into our drawing (although we highly encourage you to visit all of our vendors since they support ISSX and help make this meeting possible). Be sure to clearly print your name on your card and deposit it into the drawing bin located immediately inside the Metropolitan Ballroom Exhibit Hall entrance during the last exhibit hall session on Wednesday, October 2 by 13:00. The drawing will be held at the ISSX Booth #606 on Wednesday, October 2 at 14:00. Prize recipients are not required to be present except for the gift card prize.

Graduate/Predoctoral and Postdoctoral Poster Awards Competition Graduate/Predoctoral presentations will be held on Monday, September 30 from 12:15 - 13:00 in the Metropolitan Ballroom Foyer. Postdoctoral presentations will be held on Tuesday, October 1 from 13:00 - 13:45 in the Metropolitan Ballroom Foyer. View the finalist posters throughout the meeting and plan to attend the Poster Awards presentation on Thursday, October 3 at 10:30 in Frontenac.

Invited Speaker Information An audio-visual technician will be available to assist speakers with loading their presentations. Speakers should bring their presentations to their assigned session room no less than 30 minutes prior to the start of their session.

Name Badges/Event Tickets Name badges are required for admission to the meeting sessions, the Exhibit Hall, and social functions. Badges also help facilitate networking and communication with your fellow attendees. If you lose your badge, we are happy to provide a replacement upon showing your photo identification to the meeting registrar. Admission to the Opening Welcome Reception is included in the full-meeting registration fee. Attendees will need their name badges to be admitted to this event. Each registrant will receive two tickets for complimentary beverages during the Opening Welcome Reception. Registered guests are provided two complimentary beverage tickets. Unregistered guests or single day registrants may purchase an admission ticket for $50 for the reception at the ISSX registration desk.

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General Information ISSX Party at the Hockey Hall of Fame (Ticketed Event) Attendees may either meet in the hotel lobby on Wednesday, October 2 at 18:45 to walk with other attendees or go directly to the Hockey Hall of Fame located a short walk from the hotel at 30 Yonge Street. Join fellow attendees for a delicious dinner in a unique venue that presents Canada’s national sport through the world’s largest collection of hockey artifacts and the fun of interactive games. Attendees can take shots at real-time goalies, stop the shots of Gretzky and Messier, call the play-by-play of some of hockey’s greatest goals, get up close and personal with the Stanley Cup in the museum’s vault, and explore the largest collection of hockey memorabilia in the world. This is the premier social event at this meeting and no better place for attendees to catch up with old friends and make new acquaintances. A separate registration fee of $100 applies. Tickets may still be available. Inquire at the ISSX registration counter in the Metropolitan Ballroom Foyer.

Student and New Investigator Reception All graduate and postgraduate students as well as postdoctoral scientists in training registered at this meeting are invited to attend a networking reception on Monday, September 30 at 18:00 in the Pier 8/9. Attendees will receive a beverage ticket and have the opportunity to make new friends and network.

Welcome Reception All meeting attendees and their registered guests are invited to attend the Welcome Reception on Sunday, September 29 from 19:30 – 21:30 in the Metropolitan Ballroom Exhibit Hall. Visit friends and colleagues and learn about exhibiting companies.

Meeting Registration/Information Hours | Metropolitan Ballroom Exhibit Hall Foyer Sunday, September 29 Monday, September 30 Tuesday, October 1 Wednesday, October 2 Thursday, October 3

07:30 – 19:00 07:30 – 18:00 07:30 – 14:30 07:30 – 16:00 08:00 – 14:00

Exhibit Schedule | Metropolitan Ballroom Exhibit Hall Sunday, September 29: Welcome Reception Monday, September 30 Tuesday, October 1 Wednesday, October 2

19:30 – 21:30 10:30 – 16:00 10:30 – 14:00 10:30 – 17:00

2013 International ISSX Awards Session | Frontenac Monday, September 30

11:00 – 12:00

Poster Presentation Schedule | Metropolitan Ballroom Exhibit Hall Monday, September 30: Posters P1 – P157 Tuesday, October 1: Posters P158 – P296 Wednesday, October 2: Posters P297 – P470

12:30 – 13:30 13:00 – 14:00 13:00 – 14:00

Poster Awards Competition | Metropolitan Ballroom Exhibit Hall Foyer Monday, September 30 – Thursday, October 3: Poster Viewing

Poster Awards Competition Presentations | Metropolitan Ballroom Exhibit Hall Foyer Monday, September 30: Graduate/Predoctoral Tuesday, October 1: Postdoctoral

12:15 – 13:00 13:00 – 13:45

2013 International Meeting Poster Awards Presentation | Frontenac Thursday, October 3

10:30 – 10:45

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Westin Harbour Castle

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Scientific Program 10:00 – 10:30 | SC2.3 IN VITRO AND IN VIVO ASSESSMENT OF DRUG TRANSPORT INTO SKELETAL MUSCLE Rommel Tirona, London Health Sciences Centre University Hospital, Department of Medicine, London, Ontario, Canada

Sunday, September 29 08:00 – 09:00 | Harbour Ballroom Foyer Short Course I and II Attendee Breakfast 09:00 – 12:00 | Harbour Ballroom C Short Course I: Metabolomic Profiling as a Tool for Identifying Novel Drug-Target Interactions Chair: David Wishart, University of Alberta, Edmonton, Alberta, Canada

10:30 – 10:50 | Harbour Ballroom Foyer Refreshment Break for Short Course II Attendees 10:50 – 11:25 | SC2.4 | INCORPORATING IN VITRO INFORMATION INTO MODELS WHICH INTEGRATE INTESTINAL AND RENAL DRUG TRANSPORT Amin Rostami-Hodjegan, University of Manchester, School of Pharmacy, Manchester, UK

09:00 – 09:40 | SC1.1 | METABOLIC PHENOTYPING TECHNOLOGIES AND THEIR EXPANDING APPLICATIONS IN MEDICINE John Lindon, Imperial College London, Department of Biological Chemistry, London, UK

11:25 – 12:00 | SC2.5 | DRUG TRANSPORT IN THE BRAIN: MODELS OF BLOOD-BRAIN BARRIER AND BRAIN PARENCHYMA Reina Bendayan, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

09:40 – 10:20 | SC1.2 | STABLE ISOTOPE RESOLVED METABOLOMICS IN CELLS, TISSUE AND ANIMAL MODELS: A TOOL FOR EVALUATING RESPONSE TO CANCER THERAPEUTIC AGENTS Andrew Lane, University of Louisville, James Graham Brown Cancer Center, Louisville, Kentucky, USA

12:00 – 13:30 | Harbour Ballroom Foyer Short Course III and IV Attendee Lunch

10:20 – 10:40 | Harbour Ballroom Foyer Refreshment Break for Short Course I Attendees

13:30 – 16:30 | Harbour Ballroom AB Short Course III: Strategies and Techniques for Predicting Human Drug Metabolism and DrugDrug Interactions Chairs: Uwe Fuhr, Uniklinik Koln, Koln, Germany; Olavi Pelkonen, University of Oulu, Oulu, Finland

10:40 – 11:20 | SC1.3 | PATHWAY INFORMED METABOLOMICS DISCOVERY PROFILING AS A TOOL FOR TARGETED PROTEOMICS ANALYSIS Theodore Sana, Agilent Technologies, Life Sciences Group, Santa Clara, California, USA

13:30 – 14:10 | SC3.1 | PREDICTING DRUG METABOLISM AND TRANSPORTER DRUG INTERACTIONS IN DRUG DISCOVERY: CHALLENGES AND NOVEL TECHNIQUES Tommy B. Andersson, AstraZeneca, R&D, Mölndal, Sweden

11:20 – 12:00 | SC1.4 | METABOLOMICS AND XENOBIOTICS David Wishart, University of Alberta, Department of Biological Sciences, Alberta, Canada

09:00 – 12:00 | Harbour Ballroom AB Short Course II: Model Systems and Methods for Assessing Uptake and Efflux of Small Molecules Chair: Reina Bendayan, University of Toronto, Toronto, ON, Canada

14:10 – 14:50 | SC3.2 | PBPK COUPLED SYSTEMS BIOLOGY MODELING FOR MECHANISTIC PREDICTIONS OF PATHWAY INTERACTIONS Frederic Bois, Université de Technologie de Compiègne, Compiègne, France

14:50 – 15:10 | Harbour Ballroom Foyer Refreshment Break for Short Course III Attendees

09:00 – 09:30 | SC2.1 | DEVELOPMENT OF NOVEL TOOLS FOR DRUG TRANSPORT ASSESSMENT Matt Soars, Bristol Myers Squibb, Metabolism and Pharmacokinetics, Wallingford, Connecticut, USA

15:10 – 15:50 | SC3.3 | TOP-DOWN MODELING OF THE DYNAMIC INHIBITION OF LIVER AND GUT WALL CYP3A BY VORICONAZOLE Sebastian Frechen, University of Cologne, Department of Pharmacology, Cologne, Germany

09:30 – 10:00 | SC2.2 | ASSESSING THE ROLE OF HEPATIC UPTAKE IN DRUG CLEARANCE PHARMACOKINETIC AND EXPERIMENTAL CONSIDERATIONS Peter Webborn, AstraZeneca R&D Charnwood, Discovery DMPK, Loughborough, UK

15:50 – 16:30 | SC3.4 | PREDICTING COMPLEX DRUG-DRUG INTERACTIONS FOR MULTIPLE INHIBITOR SYSTEMS AND MULTIPLE INHIBITED PATHWAYS Nina Isoherranen, University of Washington, School of Pharmacy, Department of Pharmaceutics, Seattle, Washington, USA

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Scientific Program 13:30 – 16:30 | Harbour Ballroom C Short Course IV: Application of Novel Mass Spectrometric Methods to Drug Metabolism and Pharmacokinetics Studies Chair: Ragu Ramanathan, QPS, Newark, Delaware, USA

Monday, September 30 09:00 – 10:30 | Frontenac Plenary Session 1: Drug-Metabolizing Enzymes as Potential Therapeutic Targets Chair: Paul Hollenberg, University of Michigan, Department of Pharmacy, Ann Arbor, Michigan, USA

13:30 – 14:10 | SC4.1 | MASS SPECTROMETRY IN A DRUG DISCOVERY SETTING: UTILITY AND ISSUES Walter Korfmacher, Genzyme/Sanofi, Waltham, Massachusetts, USA

09:00 – 09:30 | S2. HUMAN CYTOCHROME P450s AS THERAPEUTIC TARGETS FOR MECHANISM-BASED INACTIVATORS Paul Hollenberg, University of Michigan, Department of Pharmacy, Ann Arbor, Michigan, USA

14:10 – 14:50 | SC4.2 | INTEGRATING DRUG METABOLISM AND PHARMACOKINETICS STUDIES USING HIGH RESOLUTION MASS SPECTROMETRY Ragu Ramanathan, QPS, Newark, Delaware, USA

09:30 – 10:00 | S3. TARGETING THE ARYLAMINE NACETYLTRANSFERASES IN CANCER Rod Minchin, University of Queensland, School of Biomedical Sciences, Queensland, Australia

14:50 – 15:10 | Harbour Ballroom Foyer Refreshment Break for Short Course IV Attendees

10:00 – 10:30 | S4. INHIBITION OF CYTOCHROME P450 17A1: TARGETING ANDROGEN PRODUCTION IN PROSTATE CANCER Emily Scott, University of Kansas, Lawrence, Kansas, USA

15:10 – 15:50 | SC4.3 | NOVEL LC-MS TECHNIQUES FOR REACTIVE METABOLITE SCREENING Raju Subramanian, Amgen, Thousand Oaks, California, USA

10:30 – 11:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters

15:50 – 16:30 | SC4.4 | LC-MS APPLICATIONS IN REGULATED BIOANALYSIS Steve Unger, Worldwide Clinical Trials, Bioanalytical Sciences, Austin, Texas, USA

11:00 – 12:00 | Frontenac 2013 International ISSX Awards Session Presented by: John O. Miners, Chair, ISSX Awards Committee and ISSX President-Elect/Secretary

18:15 – 18:45 | Frontenac Opening Welcome Address and Cultural Presentation Denis Grant, 10th International ISSX Meeting Chair; Bill Smith, ISSX President

2013 R.T. Williams Distinguished Scientific Achievement Award Presentation and Lecture Yuichi Sugiyama, Ph.D.

18:45 – 19:30 | Frontenac Keynote Lecture S1. SYSTEMS PHARMACOLOGY – SYSTEMS BIOLOGY MEETS DRUG DISCOVERY & DEVELOPMENT Douglas A. Lauffenburger, Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, Massachusetts, USA

2013 Frederick J. Di Carlo Distinguished Service Award Presentation to Robert P. Hanzlik, Ph.D.

12:00 – 13:30 | Metropolitan Ballroom Lunch on Own, Poster Presentations, Visit Exhibitors 12:15 – 13:00 | Metropolitan Ballroom Foyer Graduate/Predoctoral Poster Awards Finalist Presentations A1 – A6

19:30 – 21:30 | Metropolitan Ballroom Opening Welcome Reception with Exhibitors

12:30 – 13:30 | Metropolitan Ballroom Poster Presentations P1 – P157: Absorption to Drug Discovery and Development

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Scientific Program 15:00 – 15:30 | S12. IMPLEMENTING PERSONALIZED MEDICINE IN AN ELECTRONIC MEDICAL RECORD ENVIRONMENT: LESSONS BEING LEARNED Dan Roden, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

13:30 – 15:30 | Frontenac Parallel Session 1: Nuclear Receptors as Regulators of Drug Metabolism and as Therapeutic Targets Co-Chairs: Ulrich Zanger, Dr. Margarete FischerBosch Institute of Clinical Pharmacology, Stuttgart, Germany; Hongbing Wang, University of Maryland, School of Pharmacy, Department of Pharmaceutical Science, Baltimore, Maryland, USA

15:30 – 16:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters 16:00 – 18:00 | Frontenac Parallel Session 3: Regulation of Drug Transporter Expression and Function Chair: Micheline Piquette-Miller, University of Toronto, Toronto, Ontario, Canada

13:30 – 14:00 | S5. ADP-RIBOSYLATION BY ARTD14 DIFFERENTIALLY MODULATES NUCLEAR RECEPTOR FUNCTION Jason Matthews, University of Toronto, Department of Pharmacology and Toxicology, Toronto, Ontario, Canada

16:00 – 16:30 | S13. EVALUATION OF DRUG TRANSPORTER REGULATION DURING DRUG DISCOVERY AND DEVELOPMENT Joseph Ware, Genentech, South San Francisco, California, USA

14:00 – 14:30 | S6. THE NUCLEAR RECEPTOR CAR AS A NOVEL THERAPEUTIC TARGET IN HEMATOLOGICAL MALIGNANCIES Hongbing Wang, University of Maryland, School of Pharmacy, Department of Pharmaceutical Science, Baltimore, Maryland, USA

16:30 – 17:00 | S14. REGULATION OF DRUG TRANSPORTERS IN LIVER BY ACTIVATION OF NUCLEAR RECEPTORS Curtis Klaassen, University of Kansas Medical Center, Kansas City, Kansas, USA

14:30 – 15:00 | S7. NUCLEAR RECEPTORS PXR AND CAR IN THE CROSSROAD OF DRUG METABOLISM AND ENERGY METABOLISM Wen Xie, University of Pittsburgh, Department of Pharmaceutical Sciences, Pittsburgh, Pennsylvania, USA

17:00 – 17:30 | S15. REGULATION OF ABC TRANSPORTERS AT THE BLOOD-BRAIN AND BLOOD-SPINAL CORD BARRIERS David Miller, NIH/NIEHS Lab of Pharmacology & Chemistry, Durham, North Carolina, USA

15:00 – 15:30 | S8. REGULATION OF DRUG METABOLISM AND ENDOGENOUS FUNCTIONS BY PPARA VERSUS CAR/PXR Ulrich Zanger, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

17:30 – 18:00 | S16. REGULATION OF DRUG TRANSPORTERS IN DISEASE Micheline Piquette-Miller, University of Toronto, Toronto, Ontario, Canada

13:30 – 15:30 | Harbour Ballroom Parallel Session 2: Pharmacogenomics and Personalized Medicine: Progress in Clinical Implementation Chair: Rachel Tyndale, University of Toronto, Toronto, Ontario, Canada

16:00 – 18:00 | Harbour Ballroom Parallel Session 4: Application of Structural Biology to the Prediction of Drug Response, Metabolism and Toxicity Chair: James Halpert, University of California, San Diego, California, USA

13:30 – 14:00 | S9. CLINICAL PHARMACOGENOMICS Munir Pirmohamed, The Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK

16:00 – 16:30 | S17. STRUCTURAL DETERMINANTS OF P450 MEDIATED METABOLISM: A MOVING TARGET Eric Johnson, Scripps Research Institute, Department of Molecular & Experimental Medicine, La Jolla, California, USA

14:00 – 14:30 | S10. CLINICAL IMPLEMENTATION OF PHARMACOGENETICS IN CHILDREN: FROM GUIDELINES TO CLINICAL DECISION SUPPORT James M. Hoffman, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

16:30 – 17:00 | S18. ARYLAMINE NACETYLTRANSFERASES STRUCTURE IN DRUG METABOLISM AND DRUG DISCOVERY Edith Sim, University of Oxford, Kingston University, Oxford and Kingston, UK

14:30 – 15:00 | S11. WARFARIN PHARMACOGENETICS - EVIDENCE AND CLINICAL IMPLEMENTATION Larisa H. Cavallari, University of Illinois at Chicago, Chicago, Illinois, USA

17:00 – 17:30 | S19. USING CRYSTAL STRUCTURES OF DRUG METABOLIZING ENZYMES IN MECHANISM-BASED MODELING FOR DRUG DESIGN Hao Sun, Pfizer, Inc., Department of Pharmacokinetics, Dynamics and Metabolism, Groton, Connecticut, USA

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Scientific Program 17:30 – 18:00 | S20. CAN WE UNDERSTAND AND PREDICT LIGAND BINDING TO A HIGHLY FLEXIBLE P450? James Halpert, University of California, San Diego, California, USA

11:30 – 12:00 | S25. ASSESSMENT AND MANAGEMENT OF ADVERSE EFFECTS AND HEPATOTOXICITY ASSOCIATED WITH THE METABOLISM OF HERBAL PRODUCTS Ge Lin, Chinese University Hong Kong, School of Biomedical Sciences, Hong Kong, China

18:00 | Pier 8/9 Student and New Investigator Reception

12:00 – 12:30 | S26. INTERACTIONS BETWEEN MEDICINAL PHYTOCHEMICALS AND DRUG METABOLISM ENZYMES (PHASES I AND II) Ling Yang, Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Liaoning, China

Registered students and postdoctoral attendees are invited to attend this reception.

19:00 | Regatta President’s Reception

12:30 – 13:00 | S27. PROGRESS AND PROMISE OF CHINESE HERBAL MEDICINES: LESSONS FROM THE FIRST EU-CHINA FRAMEWORK PROGRAMME PROJECT GP-TCM Olavi Pelkonen, University of Oulu, Pharmacology & Toxicology, Oulu, Finland

By invitation.

Tuesday, October 1 09:00 – 10:30 | Frontenac Plenary Session 2: Utility of Genetic and Epigenetic Technologies in Drug Development and Safety Assessment Chair: Ann Daly, Newcastle University, Institute of Cellular Medicine, Medical School, Newcastle Upon Tyne, UK

11:00 – 13:00 | Harbour Ballroom Parallel Session 6: Cell Type Specific Mechanisms of Adverse Drug Reactions Chair: Michael Aleo, Pfizer, Global Research and Development, Groton, Connecticut, USA

09:00 – 09:30 | S21. APPLICATION OF NEXT GENERATION SEQUENCING TO PREDICTION OF SERIOUS ADVERSE DRUG REACTIONS Thomas J. Urban, Duke University Medical Center, Durham, North Carolina, USA

11:00 – 11:30 | S28. IN VITRO APPROACHES TO DETECT DRUG INDUCED ORGAN TOXICITIESLEARNINGS AND FUTURE PERSPECTIVE Michael Aleo, Pfizer, Global Research and Development, Groton, Connecticut, USA

09:30 – 10:00 | S22. GENETICS AND DRUG REPOSITIONING Philippe Sanseau, GlaxoSmithKline, Computational Biology, Stevenage, UK

11:30 – 12:00 | S29. REACTIVE METABOLITE FORMATION IN THE SKIN AND THE MECHANISM BY WHICH IT CAUSES A SKIN RASH Jack Uetrecht, University of Toronto, Faculty of Pharmacy, Toronto, Ontario, Canada

10:00 – 10:30 | S23. IMMUNOGENETIC RISK FACTORS FOR ADVERSE DRUG REACTIONS AND THE UNDERLYING MECHANISMS Yuan-Tsong Chen, Academia Sinica, Institute of Biomedical Sciences, Taipei, Taiwan

12:00 – 12:30 | S30. ROLE OF SPECIES- AND CELL TYPE-SPECIFIC EXPRESSION OF MEMBRANE TRANSPORTERS IN NEPHROTOXICITY Lawrence Lash, Wayne State University School Of Medicine, Department of Pharmacology, Detroit, Michigan, USA

10:30 – 11:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters

12:30 – 12:45 | P29. ATP METABOLISM IN RBC AS IN VIVO BIOMARKER FOR CARDIOVASCULAR TOXICITY Pollen K. F. Yeung, College of Pharmacy Dalhousie University, Halifax, Nova Scotia, Canada

11:00 – 13:00 | Frontenac Parallel Session 5: Metabolism, Pharmacokinetics and Interactions of Traditional Medicines and Natural Products Co-Chairs: Chuan Li, SIMM, Shanghai, China; Ge Lin, Chinese University Hong Kong, School of Biomedical Sciences, Hong Kong, China

12:45 – 13:00 | P442. TOWARDS A MORE PREDICTIVE MODEL: EFFECT OF TELMISARTAN ON TAUROCHOLATE DISPOSITION IN B-CLEAR® CRYOPRESERVED SANDWICH-CULTURED HEPATOCYTES COMPARED TO BSEP-EXPRESSING MEMBRANE VESICLES Tracy L. Marion, Qualyst Transporter Solutions, Durham, North Carolina, USA

11:00 – 11:30 | S24. ADME/PK STUDIES OF HERBAL MEDICINES AND WHAT WE LEARNED FROM THEM Chuan Li, SIMM, Shanghai, China

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Scientific Program 12:00 – 12:30 | S36. OPTIMIZING DELIVERY OF HER2-TARGETED LIPOSOMAL DOXORUBICIN (MM302) THROUGH IMAGING, COMPUTATIONAL ANALYSES AND EXPERIMENTATION Bart Hendriks, Merrimack Pharmaceuticals, Cambridge, Massachusetts, USA

13:00 – 14:00 | Metropolitan Ballroom Lunch on Own, Poster Presentations, Visit Exhibitors 13:00 – 13:45 | Metropolitan Ballroom Foyer Postdoctoral Poster Awards Finalist Presentations A7 – A12

12:30 – 13:00 | S37. DRUG TARGETING WITH NANOPARTICLES Arto Urtti, University of Helsinki, Helsinki, Finland

13:00 – 14:00 | Metropolitan Ballroom Poster Presentations P158 – P296: Drug Interaction to Metabolic Profiling

11:00 – 13:00 | Harbour Ballroom Parallel Session 8: Use of PB-PK Modeling in Pharmaceutical Safety Assessment Chair: Aleksandra Galetin, University of Manchester, Manchester, UK

14:00 | Free Afternoon in Toronto

Wednesday, October 2 09:00 – 10:30 | Frontenac Plenary Session 3: Identification and Use of Novel Biomarkers for Xenobiotic-Induced Toxicity Chair: David Riddick, University of Toronto, Toronto, Ontario, Canada

11:00 – 11:30 | S38. TRANSLATIONAL MODELING AND SAFETY ASSESSMENT OF TRANSPORTERMEDIATED PHARMACOKINETICS AND DRUG-DRUG INTERACTIONS Aleksandra Galetin, University of Manchester, Manchester, UK

09:00 – 09:30 | S31. MECHANISTIC BIOMARKERS OF DRUG-INDUCED LIVER AND KIDNEY INJURY B. Kevin Park, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK

11:30 – 12:00 | S39. COUPLING IN VITRO STUDIES AND PBPK MODELING TO PREDICT HUMAN SAFETY AND EFFICACY Harvey Clewell, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA

09:30 – 10:00 | S32. INSIGHTS FROM HEALTHY VOLUNTEER STUDIES Paul Watkins, Hamner-University of North Carolina Institute for Drug Safety Sciences, Research Triangle Park, North Carolina, USA

12:00 – 12:30 | S40. PHYSIOLOGICALLY-BASED TOXICOKINETIC MODELING AS A TOOL TO SUPPORT RISK ASSESSMENT Ursula Gundert-Remy, Drug Commission of the German Medical Association, Berlin, Germany

10:00 – 10:30 | S33. DNA AND PROTEIN ADDUCTS AS BIOMARKERS OF EXPOSURE TO ENVIRONMENTAL AND DIETARY TOXICANTS Robert Turesky, Wadsworth Center, Niskayuna, New York, USA

12:30 – 12:45 | P264. TRANSLATIONAL PBPK MODELING AND SIMULATION OF THE HEPATIC DISPOSITION OF ACTIVELY TRANSPORTED DRUGS BASED ON INDIVIDUAL TRANSPORTER ASSAYS Evita van de Steeg, TNO, Zeist, the Netherlands

10:30 – 11:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters

12:45 – 13:00 | P458. DRUG ACCUMULATION IN ALVEOLAR MACROPHAGES: ASSESSMENT OF UPTAKE AND LYSOSOMAL DISTRIBUTION IN VITRO Ayse Ufuk, University of Manchester, Manchester, UK

11:00 – 13:00 | Frontenac Parallel Session 7: Targeted Drug Delivery for Enhanced Therapy Chair: Christine Allen, University of Toronto, Toronto, Ontario, Canada

13:00 – 14:30 | Metropolitan Ballroom Lunch on Own, Poster Presentations, Visit Exhibitors 13:00 – 14:00 | Metropolitan Ballroom Poster Presentations P297 – P470: Metabolism to Transporters

11:00 – 11:30 | S34. THE EPR EFFECT AND BEYOND FOR CANCER SELECTIVE DRUG DELIVERY FOR TREATMENT AND IMAGING USING NANOMEDICINE Hiroshi Maeda, Sojo University, Ikeda, Japan 11:30 – 12:00 | S35. ACCESSING THE POWERHOUSE OF THE MAMMALIAN CELL WITH MITOCHONDRIAPENETRATING PEPTIDES Shana Kelley, University of Toronto, Toronto, Ontario, Canada

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Scientific Program 16:15 – 16:30 | P60. USING TARGETED QUANTITATIVE PROTEOMICS TO BETTER UNDERSTAND VARIABILITY OF THE GLUCURONIDATION PATHWAY Guillaume Margaillan, Laval University, Quebec City, Quebec, Canada

14:30 – 16:30 | Frontenac Parallel Session 9: Regulatory Perspectives in Drug-Drug Interactions and Metabolites in Safety Testing Chair: Greg Slatter, Amgen, Inc., Seattle, Washington, USA

16:30 – 17:00 | Metropolitan Ballroom Refreshment Break, Visit Exhibitors, View Posters

14:30 – 15:00 | S41. SCIENTIFIC AND REGULATORY PERSPECTIVES ON DRUG INTERACTION EVALUATION DURING DRUG DEVELOPMENT Lei Zhang, FDA, CDER, Office of Clinical Pharmacology, Silver Spring, Maryland, USA

19:00 – 22:00 | ISSX Party at the Hockey Hall of Fame (Ticketed Event) Bring your ticket and meet in the hotel lobby at 18:45 for a short group walk to the Hockey Hall of Fame.

15:00 – 15:30 | S42. THE 2012 EMA DDI GUIDELINE: THE MOST IMPORTANT UPDATES AND POSTADOPTION EXPERIENCES Eva Gil Berglund, Medical Products Agency, Uppsala, Sweden

Thursday, October 3 08:30 – 09:00 | Metropolitan Ballroom Foyer General Session: Introduction of the 11th International ISSX Meeting in Busan, Korea Meeting Organizing Committee Chairman, Jae-Gook Shin, Professor of Pharmacology/Clinical Pharmacology, Inje University, Busan, Korea

15:30 – 16:00 | S43. AN INDUSTRY PERSPECTIVE AND EXPERIENCE ON THE MOST RECENT REGULATORY DDI GUIDELINES Thomayant Prueksaritanont, Merck, Preclinical DMPK, West Point, Pennsylvania, USA 16:00 – 16:30 | S44. STRATEGIES TO ASSESS HUMAN METABOLISM OF NCES - 5 YEARS AFTER THE MIST GUIDANCES Greg Slatter, Amgen, Inc., Seattle, Washington, USA

09:00 – 10:30 | Frontenac Plenary Session 4: Genetically Modified Animal Models for Predicting Human Drug Disposition and Response Chair: Xinxin Ding, Wadsworth Center, New York State Department of Health, Albany, New York, USA

14:30 – 16:30 | Harbour Ballroom Parallel Session 10: Toxicogenomic and Metabolomic Profiling: Current Status and Future Utility in Assessing Drug Efficacy and Safety Chair: Tim Zacharewski, Michigan State University, East Lansing, Michigan, USA

09:00 – 09:30 | S48. PREGNANE X RECEPTOR AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR α HUMANIZED MICE Frank Gonzalez, National Cancer Institute, Laboratory of Metabolism, Bethesda, Maryland, USA

14:30 – 15:00 | S45. INTEGRATED EXAMINATION OF AH RECEPTOR-MEDIATED HEPATIC FAT ACCUMULATION Tim Zacharewski, Michigan State University, East Lansing, Michigan, USA

09:30 – 10:00 | S49. THE ROLE OF INTESTINAL AND HEPATIC GLUCURONIDATION IN CHEMOTHERAPY INDUCED TOXICITY BY IRINOTECAN (CPT-11) Robert Tukey, University of California, San Diego, La Jolla, California, USA

15:00 – 15:30 | S46. PHARMACOMETABOLOMICS: GLOBAL BIOCHEMICAL APPROACH FOR MAPPING DRUG EFFECTS Rima Kaddurah-Daouk, Duke University, Durham, North Carolina, USA

10:00 – 10:30 | S50. MOUSE MODELS FOR DRUG TRANSPORTERS John Schuetz, St. Jude Children’s Research Hospital, Pharmaceutical Science, Memphis, Tennessee, USA

15:30 – 16:00 | S47. MECHANISTIC UNDERSTANDING AND BIOMARKERS FOR DRUG TOXICITY USING METABOLOMICS Lining Guo, Metabolon, Durham, North Carolina, USA

10:30 – 10:45 | Frontenac 2013 International Meeting Poster Awards Presentation Presented by Denis Grant

16:00 – 16:15 | P24. REACTOME KNOWLEDGEBASE: A PLATFORM FOR PATHWAY AND NETWORK ANALYSIS Robin Haw, OICR, Toronto, Ontario, Canada

10:45 – 11:00 | Frontenac Foyer Refreshment Break

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Scientific Program 11:00 – 13:00 | Frontenac Parallel Session 11: Tissue Imaging and Distribution Studies in Drug Development Chair: Yasuyoshi Watanabe, RIKEN Center for Life Science Technologies, Kobe, Japan 11:00 – 11:30 | S51. MOLECULAR IMAGING FOR DRUG DEVELOPMENT Yasuyoshi Watanabe, RIKEN Center for Life Science Technologies, Kobe, Japan 11:30 – 12:00 | S52. MOLECULAR IMAGING FOR PHARMACOKINETICS Tomotaka Shingaki, RIKEN Center for Life Science Technologies, Kobe, Japan 12:00 – 12:30 | S53. MOLECULAR IMAGING OF DRUG TARGET MOLECULES Tetsuya Suhara, National Institute of Radiological Science, Chiba, Japan

Download the 10th International ISSX Meeting App.

12:30 – 13:00 | S54. MALDI-IMAGING MS: A GATEWAY TO TRANSLATIONAL DRUG DEVELOPMENT Stephen Castellino, GlaxoSmithKline, PTS DMPK, Research Triangle Park, North Carolina, USA

11:00 – 13:00 | Harbour Ballroom Parallel Session 12: Development and Uses of Hepatocyte-Derived and Hepatocyte-Like Cells for Predicting Human Drug Metabolism Chair: Martine Daujat-Chavanieu, INSERM, Montpellier, France

www.iss.org/2013app

11:00 – 11:30 | S55. MODELING HEPATIC DEVELOPMENT, METABOLIC DISORDERS AND DRUG REACTIVITY USING HEPATIC-LIKE CELLS Nicholas Hannan, University of Cambridge, Cambridge, UK 11:30 – 12:00 | S56. INDUSTRIAL PRODUCTION OF FUNCTIONAL HUMAN PLURIPOTENT STEM CELL DERIVED HEPATOCYTES: APPLICATIONS AND COMPARISON TO OTHER HEPATOCYTE MODELS Petter Björquist, Cellectis Stem Cells, Cellartis AB, Göteborg, Sweden 12:00 – 12:30 | S57. GENERATION OF METABOLICALLY FUNCTIONING HEPATOCYTES FROM HUMAN PLURIPOTENT STEM CELLS BY TRANSDUCTION OF FOXA2 AND HNF1α Hiroyuki Mizuguchi, Osaka University, Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka, Japan 12:30 – 13:00 | S58. IMPACT OF ENVIRONMENTALS ON THE DIFFERENTIATION OF HUMAN ADULT HEPATIC PROGENITORS Martine Daujat-Chavanieu, INSERM, Montpellier, France

13:00 | Frontenac Meeting Closing Remarks Denis Grant, 10th International ISSX Meeting Chair; Bill Smith, ISSX President 20


Poster Information Poster Awards Finalist Abstract Presentation Schedule | Metropolitan Ballroom Foyer Category GRADUATE/ PREDOCTORAL

Set-up Time

Poster Viewing

Authors Present

Dismantle Time

Monday, September 30

Monday September 30 07:30 – 09:00

Monday, September 30 – Thursday, October 3

POSTDOCTORAL

12:15 – 13:00 Tuesday, October 1

Thursday October 3 11:00 – 12:00

13:00 – 13:45

Poster Abstract Presentation Schedule | Metropolitan Ballroom Category

Set-up Time

Poster Viewing

POSTER SESSION 1 September 30

Monday September 30 07:30 – 09:00

Monday September 30 10:30 – 16:00

Odd Numbers: 12:30 – 13:00 Even Numbers: 13:00 – 13:30

POSTER SESSION 2 October 1

Tuesday October 1 07:30 – 09:00

Tuesday October 1 10:30 – 14:00

Odd Numbers: 13:00 – 13:30 Even Numbers: 13:30 – 14:00

POSTER SESSION 3 October 2

Wednesday October 2 07:30 – 09:00

Wednesday October 2 10:30 – 17:00

Odd Numbers: 13:00 – 13:30 Even Numbers: 13:30 – 14:00

Authors Present Abstracts P1 – P157

Abstracts P158 – P296

Abstracts P297 – P470

Dismantle Time Monday September 30 18:00 – 19:00 Tuesday October 1 14:00 – 15:00 Wednesday October 2 17:00 – 18:00

OUT OF COURTESY TO THE AUTHORS, PLEASE REFRAIN FROM TAKING PHOTOGRAPHS OR VIDEO RECORDING. Posters will be attended during designated presentation times. This is your opportunity to ask authors about their research. To obtain a copy of specific information that is being presented, contact the author directly. Finalists Graduate/Predoctoral Award Competition Finalists Postdoctoral Fellow Award Competition

A1 – A6 A7 – A12

Analytical Bioavailability Bioinformatics Biomarkers Blood-Brain Barrier Carcinogenesis/Mutagenesis Clearance Prediction Conjugation Reactions and Enzymes CYPs Endogenous Functions Cytochrome P450 Differences in Metabolism (species, gender, age, diseases) Disposition DNA Damage and Repair Drug Delivery Drug Discovery and Development Drug Interaction

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P1 – P14 P15 – P23 P24 – P25 P26 – P38 P39 – P46 P47 – P50 P51 – P54 P55 – P67 P68 – P69 P70 – P110 P111 – P119 P120 – P125 P126 P127 – P128 P129 – P157 P158 – P175


Poster Information Environmental Toxicity Enzyme Bioengineering Enzyme Induction Enzyme Inhibition/Inactivation Extrahepatic Metabolism Gene Expression and Regulation Genomics/Metabolomics/Proteomics Hepatocytes Herbal Medicine-Active Compounds Herb-Drug Interactions High-throughput Techniques in silico in vitro/in vivo Extrapolation in vitro Techniques Mechanisms of Xenobiotic Toxicities Metabolic Profiling Metabolism Non-P450 Phase I Enzymes Oxidative Stress Pharmacogenetics/Pharmacoepigenetics Pharmacokinetics and Pharmacodynamics Receptors/Nuclear Receptors Risk Assessment siRNA/microRNA Stem Cell Research Stereoselective Metabolism Therapy Transporters

P176 – P183 P184 P185 – P189 P190 – P205 P206 – P208 P209 – P225 P226 – P229 P230 – P235 P236 – P239 P240 – P245 P246 – P250 P251 – P256 P257 – P264 P265 – P273 P274 – P291 P292 – P296 P297 – P330 P331 – P338 P339 – P343 P344 – P365 P366 – P395 P396 – P400 P401 P402 P403 P404 – P406 P407 – P409 P410 – P470

5th Asia Pacific ISSX Meeting | Tianjin, China May 9 – 12, 2014 Call for Abstracts We encourage all researchers involved in the investigation of drug metabolism, pharmacology, toxicology, molecular biology, and other related disciplines to consider submitting an abstract for a poster presentation at the 5th Asia Pacific ISSX Meeting. This meeting will provide the scientific community with a wonderful opportunity to showcase work being done in a variety of areas and to network with other researchers. Please visit www.issx.org/5AP/Abstracts to submit an abstract for poster presentation. The abstract submission deadline is Friday, January 31, 2014 at 11:59 p.m. Eastern Time (U.S.)

19th North American ISSX Meeting /29th JSSX Meeting | San Francisco, CA, USA October 19 – 23, 2014 Call for Abstracts will open Monday, January 6, 2014

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Poster Details ANALYTICAL (P1 – P14)

GRADUATE/PREDOCTORAL POSTER FINALISTS (A1 – A6)

P1. DEVELOPMENT OF A NOVEL QUANTITATIVE LC-MS/MS BASED ASSAY FOR ALBUMIN-ACETAMINOPHEN ADDUCTS Lekha Sleno, Université du Québec À Montréal, Montreal, QC, Canada P2. APPLICABILITY OF DIFFERENT SOFT NUCLEOPHILES FOR SCREENING REACTIVE METABOLITES RESULTING FROM MICROSOMAL ACTIVATION OF FURAN MIXTURES AND CIGARETTE SMOKE Arno Knorr, Philip Morris Products S.A., Neuchatel, Switzerland P3. COMPARISON OF DRIED BLOOD SPOT AND PLASMA CONCENTRATIONS OF NIFEDIPINE IN HEALTHY VOLUNTEERS Sara K. Quinney, Indiana University, Indianapolis, IN, USA P4. MULTIPLE-DOSE PHARMACOKINETICS OF PIPERPHENTONAMINE HYDROCHLORIDE, A NOVEL CALCIUM SENSITIZER, IN HEALTHY VOLUNTEERS Min Li, Beijing Hospital, the Ministry of Health, Beijing, China P5. CONTRIBUTION OF QUANTITATIVE MASS SPECTROMETRY IMAGING (MSI) IN PHARMACEUTICAL FIELD: APPLICATION TO DRUG AND PEPTIDE ANALYSIS IN TISSUE Jonathan Stauber, Imabiotech, Loos, France P6. DETERMINATION OF GDC-0068 AND ITS METABOLITE IN HUMAN PLASMA USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY COUPLED TO MASS SPECTROMETRY Yuzhong Deng, Genentech Inc., South San Francisco, CA, USA P7. APPLICATION OF DRIED PLASMA SPOT SAMPLING IN COMBINATION WITH LC-MS/MS METHOD FOR PHARMACOKINETIC STUDIES OF FOUR IRIDOID GLYCOSIDES IN DOGS Guangli Wei, Tianjin Institute of Pharmaceutical Research, Tianjin, China P8. OPTIMIZATION OF SAMPLE PREPARATION METHOD FOR PROTEIN DRUG QUANTIFICATION IN HUMAN SERUM BY LC-MS/MS Katsuaki Ito, Teijin Pharma Limited, Hino, Japan P9. IN VITRO METABOLISM OF CAPSAICIN AND DIHYDROCAPSAICIN: POSSIBLE BIOMARKERS AFTER PEPPER SPRAY EXPOSURE Mia Halme, VERIFIN, Institute for Verification of the Chemical Weapon Convention, Helsinki, Finland P10. A SIMULTANEOUS CHROMATOGRAPHIC ANALYSIS OF TYPICAL DRUGS AND METABOLITES FOR PSYCHOTIC DISORDERS Maho Okubo, Showa Pharma Univ., Machida, Japan P11. IONIC LIQUID GCXGC-TOF-MS APPROACH FOR GENERIC SCREENING OF AEROSOL CONSTITUENTS IN AQUEOUS TOBACCO AEROSOL FRACTIONS AND ANALYSIS OF MICROSOMAL INCUBATES Quentin Dutertre, Philip Morris Products S.A., Neuchatel, Switzerland P12. DETERMINATION OF BEPOTASTINE BESILATE IN HUMAN PLASMA AND URINE SAMPLES BY LC/MS/MS AND ITS APPLICATION TO CLINICAL PHARMACOKINETIC STUDY OF CHINESE VOLUNTEERS Aixin Shi, Beijing Hospital, the Ministry of Health, Beijing, China P13. ENANTIOMERIC DETERMINATION OF LANSOPRAZOLE ENANTIOMERS IN DOG PLASMA BY LC-MS/MS WITH ACHIRAL-CHIRAL COLUMN –SWITCHING Jingkai Gu, Jilin University, Changchun, China

A1. CYP2B6*6 ALLELE ALTERS KETAMINE'S PHARMACOKINETICS IN CHRONIC PAIN PATIENTS AND METABOLISM IN VITRO Yibai Li, University of Adelaide A2. GLUICAT: A NOVEL LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY-BASED METHOD FOR PROFILING PROTEIN GLUTATHIONYLATION Chun Yip Chan, National University of Singapore A3. THE IMPORTANCE OF 5Α-REDUCTASE GENE POLYMORPHISMS ON CIRCULATING AND INTRAPROSTATIC ANDROGENS IN PROSTATE CANCER Isabelle Laverdiere, Laval University A4. PHARMACOGENOMIC PREDICTORS OF GRAFT-VSHOST DISEASE AND SURVIVAL AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CANCER PATIENTS Isabelle Laverdiere, Laval University A5. ENHANCED SYNTHESIS OF CHOLESTEROL AND BILE ACID IN THE LIVER OF CYP3A-KNOCKOUT MICE Mari Hashimoto, Chiba University A6. DUAL ROLE FOR UDP GLUCURONOSYLTRANSFERASE (UGT) 1A SPLICE VARIANT FORMS 2 (I2) IN DEFINING PHARMACOLOGICAL RESPONSE AND IN THE OXIDATIVE STRESS PATHWAY Mélanie Rouleau, Laval University

POSTDOCTORAL POSTER FINALISTS (A7 – A12) A7. INTERINDIVIDUAL VARIABILITY OF CYP2C19CATALYZED DRUG METABOLISM DUE TO DIFFERENCES IN THE DIPLOTYPES Yoshiyuki Shirasaka, University of Washington A8. DETERMINATION OF SPECIES-DIFFERENCE IN MICROSOMAL METABOLISM OF AMITRIPTYLINE USING A PREDICTIVE MRM-IDA-EPI METHOD Soo Jin Oh, Korea Research Institute of Bioscience and Biotechnology A9. ABCC11/MRP8 POLYMORPHISMS AFFECT 5FLUOROURACIL-INDUCED SEVERE LEUCOPENIA AND HEPATIC EXPRESSION Tarek M. S. Mohamed, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology A10. ABCC5 MODULATES SYSTEMIC EXPOSURE OF SN-38GLUCORONIDE IN METASTATIC COLORECTAL CANCER PATIENTS TREATED WITH IRINOTECAN Wendy A. Teft, The University of Western Ontario A11. ROLE OF KRÜPPEL-LIKE FACTOR 9 (KLF9) IN CYTOCHROME P450 2D6 (CYP2D6) INDUCTION DURING PREGNANCY Kwi Hye Koh, University of Illinois at Chicago A12. ADME-RELATED MICRORNAS IN HUMAN LIVER: ASSOCIATION WITH NON-GENETIC FACTORS AND EFFECTS ON DRUG METABOLISM Jessica K. Rieger, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology

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Poster Details P14. SIMULTANEOUS DETERMINATION OF CYCLOPHOSPHAMIDE AND DEXAMETHASONE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY WITH UV WAVELENGTH SWITCHING Makhotso Rose Lekhooa, University of the Free State, Bloemfontein, South Africa

P25. ADDRESSING TOXICITY RISK WHEN DESIGNING AND SELECTING COMPOUNDS IN EARLY DRUG DISCOVERY Nicholas W. Foster, Optibrium Ltd., Cambridge, United Kingdom

BIOMARKERS (P26 – P38) P26. CYP2E1 EXPRESSION AND ACTIVITY IN THE PERIPHERAL BLOOD MONONUCLEAR CELLS OF CIGARETTE SMOKERS Catherine A. Wassenaar, University of Toronto, Toronto, ON, Canada P27. THE DIFFERENCE IN THE METABOLITE PROFILES BETWEEN PLASMA AND SERUM, AGES OR SEXES, AND THEIR INTER-INDIVIDUAL VARIATIONS IN HUMAN SUBJECTS Kosuke Saito, National Institute of Health Sciences, Tokyo, Japan P28. THE ROLE OF ALPHA 1-ACID GLYCOPROTEIN (AAG) AS A BIOMARKER FOR ARRY-520 EXPOSURE Karin D. Brown, Array BioPharma Inc., Boulder, CO, USA P29. ATP METABOLISM IN RBC AS IN VIVO BIOMARKER FOR CARDIOVASCULAR TOXICITY Pollen K. F. Yeung, Dalhousie University, Halifax, NS, Canada P30. ISONIAZID-INDUCED LIVER INJURY IN HUMANS IS IMMUNE-MEDIATED AND NOT “METABOLIC IDIOSYNCRASY” Imir G. Metushi, Faculty of Medicine, University of Toronto, Toronto, ON, Canada P31. COMPARATIVE STUDY OF EXPRESSION OF SMAD3 IN ORAL LICHEN PLANUS AND NORMAL ORAL MUCOSA Shimae Nafarzadeh, Assistant professor,Oral Pahology department,Babol medical school, Babol, Iran P32. DNA METHYLATION PROFILES OF MATERNAL PERIPHERAL BLOOD AND INTRAUTERINE GROWTH RESTRICTION Jie Ping, Medical School of Wuhan University, Wuhan, China P33. QUANTITATIVE TARGETED ABSOLUTE PROTEOMICS OF THE MALIGNANT BRAIN TUMORS TOWARDS MOLECULAR-TARGETED CHEMOTHERAPY Tetsuya Terasaki, Tohoku University, Sendai, Japan P34. PLASMA DIHYDROURACIL/URACIL RATIO AS A PREDICTIVE BIOMARKER FOR THE EFFECT AND PHARMACOKINETICS OF 5-FLUOROURACIL IN COLORECTAL TUMOR GROWTH Yukako Ito, Kyoto Pharmaceutical University, Kyoto, Japan P35. EVALUATION OF 4BETA-HYDROXYCHOLESTEROL AS AN ENDOGENOUS BIOMARKER OF CYP3A IN CYNOMOLGUS MONKEYS Sylvia Zhao, Janssen Research & Development, Shanghai, China P36. AD HOC CAFFEINE PHENOTYPING FOR CYP1A2, CYP2A6, XO AND NAT2 ACTIVITY IN ADULTS AND CHILDREN Yvonne S. Lin, University of Washington, Seattle, WA, USA P37. LIPIDOMIC PROFILES IN BLOOD FROM FASTED HEALTHY ADULTS VARY BETWEEN PLASMA AND SERUM AND BY SUBJECT'S GENDERS AND AGES Keiko Maekawa, National Institute of Health Sciences, Tokyo, Japan P38. URINARY METABOLIC PATTERN OF VINCLOZOLIN IN ADULT MALE RAT M. Cruz-Hurtado, Cinvestav-IPN, México D.F., Mexico

BIOAVAILABILITY (P15 – P23) P15. EFFECT OF FOOD INTAKE ON THE PHARMACOKINETICS OF CATALPOL IN BEAGLE DOGS Changxiao Liu, Tianjin Institute of Pharmaceutical Research, Tianjin, China P16. IDENTIFICATION OF ALTERED PROTEIN BINDING OF DEXAMETHASONE IN THE PRESENCE OF SUGAMMADEX Ian S. Westley, The Queen Elizabeth Hospital, Woodville, Australia P17. EXTENSIVE METABOLISM AND P-GLYCOPROTEINMEDIATED EFFLUX OF Y101, AN ANTI-HBV AGENT, MAY CONTRIBUTE TO UNDERSTANDING THE INCOMPLETE BIOAVAILABILITY IN RATS Huirong Fan, Tianjin Institute of Pharmaceutical Research, Tianjin, China P18. EVALUATION OF INTESTINAL PERMEABILITY OF PROTOPANAXATRIOL AND PROTOPANAXADIOL USING CACO-2 CELL MONOLAYER Qi Chang, Institute of Medicinal Plant Development, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China P19. SCALING FACTORS FOR INTESTINAL METABOLISM IN DOGS: EXAMINING INTERINDIVIDUAL AND REGIONAL VARIABILITY, AND CORRELATIONS TO HEPATIC SCALING FACTORS Oliver J. D. Hatley, Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester, United Kingdom P20. COMPARISON OF THE PHARMACOKINETICS BETWEEN TWO VORICONAZOLE FORMULATIONS AND THE EFFECT OF CYP2C19 POLYMORPHISMS ON VORICONAZOLE EXPOSURE HyeKyung Han, Seoul National University College of Medicine and Hospital, Seoul, South Korea P21. AN INTEGRATED APPROACH OF IN VITRO PHYSIOLOGICALLY RELEVANT INTESTINAL MODELS AND PBPK MODELING TO PREDICT ORAL BIOAVAILABILITY IN HUMANS Evita van de Steeg, TNO, Zeist, Netherlands P22. COMPARISON OF LOCAL PHARMACOKINETIC MODELS OF GASTROINTESTINAL ABSORPTION: TRANSLOCATION MODEL AND ACAT MODEL (GASTROPLUSTM) Hirotaka Ando, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan P23. BIOTRANSFORMATION OF POLYPHENOLS AND THEIR ANTIOXIDANT ACTIVITY AFTER DIGESTION IN THE COMPUTER CONTROLLED DYNAMIC HUMAN GASTROINTESTINAL MODEL Shima Sadeghi Ekbatan, McGill University, Montreal, QC, Canada

BIOINFORMATICS (P24 – P25) P24. REACTOME KNOWLEDGEBASE: A PLATFORM FOR PATHWAY AND NETWORK ANALYSIS Robin Haw, OICR, Toronto, ON, Canada

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Poster Details BLOOD-BRAIN BARRIER (P39 – P46)

CLEARANCE PREDICTION (P51 – P54)

P39. HBMEC/CIΒ, NEWLY-DEVELOPED CONDITIONALLY IMMORTALIZED HUMAN BRAIN MICROVASCULAR ENDOTHELIAL CELLS, EXPRESS VARIOUS RECEPTORS INVOLVED IN TRANSCYTOSIS AT THE BLOOD-BRAIN BARRIER Tomomi Furihata, Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba-Shi, Japan P40. EVALUATION OF CASSETTE DOSING TO SCREEN CNS COMPOUNDS IN DRUG DISCOVERY Gauri Deshmukh, Genentech Inc., South San Francisco, CA, USA P41. EVALUATION OF CASSETTE DOSING TO ENHANCE THE THROUGHPUT FOR RAT BRAIN MICRODIALYSIS STUDIES IN DRUG DISCOVERY Gauri Deshmukh, Genentech Inc., South San Francisco, CA, USA P42. ROLE OF PANNEXIN AND CONNEXIN HEMICHANNELS IN THE PATHOLOGICAL HUMAN BLOOD-BRAIN BARRIER TRANSPORT Masanori Tachikawa, Tohoku University, Sendai, Japan P43. EXPRESSIONAL AND FUNCTIONAL CHARACTERIZATION OF A RAT PRIMARY CO-CULTURED BLOOD-BRAIN BARRIER MODEL Houfu Liu, GSK R&D China, Shanghai, China P44. COMBINED CONTRIBUTIONS OF EPILEPTIC SEIZURE AND ANTI-EPILEPTIC DRUG INDUCTION TO OVEREXPRESSION OF P-GLYCOPROTEIN AT BRAIN OF PHARMACORESISTANT EPILEPSY Xiao-dong Liu, China Pharmaceutical University, Nanjing, China P45. POTENTIAL EFFECT OF ANTI-INFLAMMATORY COMPOUNDS ON HIV-1 GP120.MEDIATED BRAIN INFLAMMATION Tamima Ashraf, University of Toronto, Toronto, ON, Canada P46. IN VITRO P-GP EFFLUX RATIO CAN PREDICT THE IN VIVO BRAIN PENETRATION REGARDLESS OF BDDCS CLASS J. Cory Kalvass, AbbVie Inc., North Chicago, IL, USA

P51. EVALUATION OF ENDOGENOUS METABOLIC MARKERS OF CYP3A ACTIVITY USING METABOLIC PROFILING AND MIDAZOLAM CLEARANCE Kwang-Hee Shin, Seoul National University, Seoul, South Korea P52. PREDICTABILITY OF PLASMA CONCENTRATION-TIME PROFILES IN HUMANS USING CHIMERIC MICE WITH HUMANIZED LIVER Seigo Sanoh, Hiroshima University, Hiroshima, Japan P53. TRANSLATIONAL RESEARCH TOOLS TO IMPROVE DRUG THERAPY IN PEDIATRICS Souzan B. Yanni, Dmpk Consultants, Inc., Chapel Hill, NC, USA P54. CROSS-VALIDATION OF PRECLINICAL TOOLS FOR HEPATIC DRUG METABOLISM: FROM SUBCELLULAR STUDIES TO IN VIVO Johan Nicolaï, KU Leuven, Leuven, Belgium

CONJUGATION REACTIONS AND ENZYMES (P55 – P67) P55. ASCORBYLATION AND GLUTATHIONYLATION OF GLUTAREDOXIN-1 BY DEHYDROASCORBATE Klaus Klarskov, Université de Sherbrooke, Sherbrooke, QC, Canada P56. UNDERSTANDING THE ROLE OF UDPGLUCURONOSYLTRANSFERASE UGT2B28 IN PROSTATE CANCER Anaïs Belledant, Pharmacogenomics Laboratory, (Québec), QC, Canada P57. INTERSYSTEM EXTRAPOLATION FACTORS (ISEF) FOR HUMAN UDP-GLUCURONOSYLTRANSFERASE (UGT) ACTIVITY: UTILITY TO ESTIMATE UGT1A1-MEDIATED FRACTIONAL CLEARANCE Jian Lin, Pfizer Global Research and Development, Groton, CT, USA P58. NOVEL ACTIVITIES OF UDP GLYCOSYLTRANSFERASE (UGT) 8 Peter I. Mackenzie, Flinders University, Adelaide, Australia P59. GENERATION OF HERITABLE MUTATIONS IN THE ZEBRAFISH SULT4A1 GENE USING TRANSCRIPTION ACTIVATOR-LIKE EFFECTOR NUCLEASES (TALENS) Frank Crittenden, University of Alabama at Birmingham, Birmingham, AL, USA P60. USING TARGETED QUANTITATIVE PROTEOMICS TO BETTER UNDERSTAND VARIABILITY OF THE GLUCURONIDATION PATHWAY Guillaume Margaillan, Université Laval, Québec, QC, Canada P61. IN VITRO SULFATION OF THREE ACTIVE CONSTITUENTS OF CHANSU BY HUMAN LIVER CYTOSOL: IMPLICATIONS ON THE MAJOR METABOLIC PATHWAYS OF BUFODIENOLIDES Ling Yang, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China P62. UDP-GLUCURONOSYLTRANSFERASE 1A1 IS THE PRINCIPAL ENZYME RESPONSIBLE FOR BAVACHININ GLUCURONIDATION IN HUMAN LIVER MICROSOMES Xia Lv, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China P63. UGT1A9 PLAYS PREDOMINANT ROLE IN GLUCURONIDATION OF SHIKONIN Ling Yang, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China

CARCINOGENESIS/MUTAGENESIS (P47 – P50) P47. ROLE OF CYP2ABFGS IN NNK BIOACTIVATION AND LUNG TUMORIGENESIS: INSIGHTS FROM A NOVEL CYP2ABFGS-NULL MOUSE Xinxin Ding, Wadsworth Center, New York State Department of Health, Albany, NY, USA P48. INFLUENCE OF SEX AND STRAIN ON HEPATOTOXIC AND INFLAMMATORY RESPONSES TO LIVER CARCINOGENS IN THE MOUSE Daniel Hanna, University of Toronto, Toronto, ON, Canada P49. CLASSIFICATION MODELS TO PREDICT CARCINOGENICITY USING ANT COLONY OPTIMIZATION AND DECISION TREES Sitarama Gunturi, Tata Consultancy Services Limited, Hyderabad, India P50. PIPERINE DOWNREGULATES HER2 EXPRESSION, LEADING TO INHIBITION OF HER2-MEDIATED PROLIFERATION, MIGRATION AND APOPTOSIS POTENTIALS IN HER2-OVEREXPRESSING BREAST CANCER CELLS Hyung Gyun Kim, Chungnam National University, Daejeon, South Korea

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Poster Details P64. GLUTATHIONE TRANSFERASE P1 (GSTP1) IS STRONGLY ASSOCIATED WITH CELLULAR MEMBRANES AND MODIFIED BY PALMITATE Vanessa Marensi, University of Alberta, Edmonton, AB, Canada P65. RECOMBINANT ARYLAMINE NACETYLTRANSFERASES OF NON-HUMAN PRIMATES AS MODELS FOR IN VITRO EVALUATION OF PHARMACEUTICAL COMPOUNDS Sotiria Boukouvala, Democritus University of Thrace, Alexandroupolis, Greece P66. A NOVEL HUMANIZED UGT2 MOUSE MODEL CONTAINING THE HUMAN UGT2 CLUSTER FOR ASSESSING DRUG GLUCURONIDATION Tsuneo Deguchi, Daiichi Sankyo Co., Ltd., Tokyo, Japan P67. REFINING THE SULT1B1 MECHANISM: IMPORTANCE OF THE HIGHLY CONSERVED DIMERIZATION DOMAIN Zachary E. Tibbs, University of Alabama at Birmingham, Birmingham, AL, USA

P77. THE ROLE OF HEPATIC CYTOCHROME P450 2A5 DURING ENDOPLASMIC RETICULUM STRESS Larry J. Morgan, University of Guelph, Guelph, ON, Canada P78. REGULATION OF CYTOCHROME P450 2A5 BY 6,7DIMETHYLESCULETIN IN MURINE HEPATOCYTES Sangsoo Daniel Kim, University of Guelph, Guelph, ON, Canada P79. THE ROLE OF CYTOCHROME P450 ENZYMES IN THE FORMATION OF EPOXYEICOSATRIENOIC ACIDS, AND MIDCHAIN, SUBTERMINAL, AND TERMINAL HYDROXYEICOSATETRAENOIC ACIDS Ahmed A. El-Sherbeni, University of Alberta, Edmonton, AB, Canada P80. DIFFERENTIAL ROLE OF CENTRAL AND PERIPHERAL D2 RECEPTORS IN THE REGULATION OF CYP METABOLIC ACTIVITY Michaela Sabova, Masaryk University, Brno, Czech Republic P81. IDENTIFICATION OF CYTOCHROME P450S INVOLVED IN THE METABOLISM OF ARACHIDONIC ACID IN HUMAN PLATELETS Eon-Jeong Shim, Inje University College of Medicine and Busan Paik hospital, Busan, South Korea P82. IMPACT OF AGE ON HEPATIC CYTOCHROME P450 OF PIGS Steven Hu, Zoetis, Inc, Kalamazoo, MI, USA P83. ABSTRACT WITHDRAWN P84. IDENTIFICATION AND CHARACTERIZATION OF A NOVEL CYP3A4 VARIANT RESULTING FROM MISSENSE MUTATION FOUND IN KIDNEY TRANSPLANTED PATIENT WITH DEFECTS IN TACROLIMUS CLEARANCE Anneke N. Werk, Institute for Clinical and Experimental Pharmacology, Kiel, Germany P85. OPTIMIZATION OF CYP KNOCK-OUT IN VIVO MODELS – RATS AND MICE Upendra A. Argikar, Novartis Institutes for Biomedical Research Inc., Cambridge, MA, USA P86. APPLICATION OF THE CYP3A4 SELECTIVE MECHANISM-BASED INACTIVATOR CYP3CIDE TO DELINEATE CYP3A4 AND CYP3A5 CONTRIBUTIONS TO THE METABOLISM OF CYP3A CLEARED DRUGS Elaine Tseng, Pfizer Global Research and Development, Groton, CT, USA P87. IC50 SHIFT ASSAY FOR DETECTING CYTOCHROME P450 TIME-DEPENDENT INHIBITION OF DRUG CANDIDATES IN DRUG DISCOVERY AND DEVELOPMENT HyunJi Jeong, SK Biopharmaceuticals, Daejeon, South Korea P88. A NEW APPROACH TO HIGH THROUGHPUT ADME ASSAY SCREENING Jing Wang, Labcyte, Inc., Sunnyvale, CA, USA P89. DEVELOPMENT OF A SELECTIVE CYP2B6 AND CELL VIABILITY DUPLEX ASSAY James J. Cali, Promega Corporation, Madison, WI, USA P90. HPLC-MS DETERMINATION OF FIVE PROBE DRUGS AND EVALUATION OF THP ENANTIOMERS ON THE ACTIVITY OF CYTOCHROME P450 ISOZYMES IN RATS Zhanying Hong, Second Military Medical University, Shanghai, China P91. PREDICTION OF CYP3A4 INDUCTION POTENTIAL WITH RIS IN HEPARG™ CELLS AT MRNA AND ACTIVITY LEVELS Jun Sun, Abbvie Inc, North Chicago, IL, USA

CYPS ENDOGENOUS FUNCTIONS (P68 – P69) P68. MICE DEFICIENT IN INTESTINAL EPITHELIUM CYTOCHROME P450 REDUCTASE HAVE ELEVATED LEVELS OF SECRETARY IMMUNOGLOBIN A AND ARE PRONE TO ACUTE TOXIN-INDUCED MUCOSAL DAMAGE Fang Xie, Wadsworth Center, NYSDOH, Albany, NY, USA P69. TRANSCRIPTOMIC AND METABOLOMIC EFFECTS OF INDIVIDUAL CYP EXPRESSION IN HEPG2 CELLS Aurelie J. Krol, INSERM U775, Paris, France

CYTOCHROME P450 (P70 – P110) P70. TOWARDS THE ABSOLUTE QUANTIFICATION OF CYP450 ISOFORMS: A PROTEOMICS STUDY Jingkai Gu, Jilin University, Changchun, China P71. EXPRESSION OF CLINICALLY RELEVANT METABOLIZING ENZYMES AND NUCLEAR RECEPTORS ALONG THE ENTIRE HUMAN INTESTINE Stefan Oswald, University of Greifswald, Greifswald, Germany P72. INDUCTION OF PROCARCINOGEN-ACTIVATING ENZYMES, CYP1A1, CYP1A2, AND CYP1B1 BY TRIMETHYL ARSINE OXIDE (TMA) IN C57BL/6 MICE Osama H. Elshenawy, University of Alberta, Edmonton, AB, Canada P73. INDUCTION OF PROCARCINOGEN-ACTIVATING ENZYMES, CYP1A1, CYP1A2, AND CYP1B1 BY TRIMETHYL ARSINE OXIDE IN C57BL/6 MICE Osama H. Elshenawy, University of Alberta, Edmonton, AB, Canada P74. ROLE OF HEPATIC AND INTESTINAL P450 ENZYMES IN THE METABOLIC ACTIVATION OF THE COLON CARCINOGEN AZOXYMETHANE IN MICE Qing-Yu Zhang, Wadsworth Center, New York State Department of Health, Albany, NY, USA P75. HUMAN LIVER S9 FRACTIONS STORED AT -80°C MAINTAIN HIGH PHASE I AND PHASE II ENZYMATIC ACTIVITIES OVER MULTIPLE FREEZE/THAW CYCLES AND FOR AT LEAST 10 YEARS David B. Buckley, XenoTech, LLC, Lenexa, KS, USA P76. EVALUATION ON THE ACTIVITIES OF CYTOCHROME P450 ISOFORMS BY COCKTAIL APPROACH IN STREPTOZOTOCIN INDUCED DIABETIC RATS Qin LI, Tianjin Medical University, Tianjin, China

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Poster Details P92. METABOLIC BIOACTIVATION OF PIPERAZINE IN ΒNAPHTHOFLAVONE AND PHENOBARBITAL OR AROCROL 1254 INDUCED RAT LIVER S9 FRACTIONS Mithat Gunduz, Novartis Institutes for Biomedical Research Inc., Cambridge, MA, USA P93. POTENTIAL OF THALIDOMIDE FOR INDUCTION OF DRUG METABOLIZING ENZYMES IN HUMAN LIVERS Norie Murayama, Showa Pharmaceutical University, Machida, Japan P94. REDUCTION OF THYROID HORMONES TRIGGERS DOWN-REGULATION OF HEPATIC CYP2B THROUGH NUCLEAR RECEPTORS CAR AND TR IN A RAT MODEL OF ACUTE STROKE Jiang Yue, Basic Medical School of Wuhan University, Wuhan, China P95. IDENTIFICATION OF POTENT CYP2D6 INHIBITORS IN NELUMBO NUCIFERA LEAVES Ye Lin hu, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China P96. STUDIES OF IN VITRO MODULATORY EFFECT OF LABISIA PUMILA ON CYP1A2, CYP2A6 AND CYP3A4 Chin Eng Ong, Monash University Sunway Campus, Selangor, Malaysia P97. DOWN-REGULATION OF TESTICULAR CYTOCHROME P450 AND RELATED ENZYMES BY ESTRADIOL IN ADULT RAT TESTIS Stelvio Bandiera, Univ of British Columbia, Vancouver, BC, Canada P98. TIME COURSE FOR THE MODULATIONS OF CYTOCHROME P450 EPOXYGENASES AFTER ISOPROTERENOL ADMINISTRATION TO INDUCE CARDIAC HYPERTROPHY Hassan Althurwi, University of Alberta, Edmonton, AB, Canada P99. REGULATION OF THE RETINOIC ACID-METABOLIZING CYP2C22 BY NITRIC OXIDE Edward T. Morgan, Emory University, Atlanta, GA, USA P100. CONSUMPTION OF A HIGH-FAT DIET DURING PREGNANCY CHANGES THE EXPRESSION OF CYTOCHROME P450 IN THE LIVERS OF INFANT MALE MICE Masataka Tajima, Hoshi University, Tokyo, Japan P101. CYP4F2 IS THE MAJOR CYTOCHROME P450 ENZYME INVOLVED IN CMX001 METABOLISM Tim Tippin, Chimerix, Inc., Durham, NC, USA P102. CROCIN INCREASES METABOLIC ACTIVITY OF CYP2C6 Gabriela Dovrtelova, Masaryk University, Brno, Czech Republic P103. CYP2E1 AND CYP2U1 PROTEIN EXPRESSION IN HUMAN AMYGDALA AND PREFRONTAL CORTEX: INFLUENCE OF ALCOHOLISM AND SMOKING Francesca Toselli, University of Queensland, Brisbane, Australia P104. 1-AMINOBENZOTRIAZOLE INEFFECTIVELY INACTIVATES CYP2C9 DUE TO PREFERENTIAL BINDING TO THE DISTAL WARFARIN BINDING SITE OF CYP2C9 Jasleen Sodhi, Genentech Inc., South San Francisco, CA, USA P105. COCULTURE OF ANTIGEN-PRESENTING CELLS AND KERATINOCYTES: MODULATION OF COMPOUND-RELATED INCREASE OF CYP1 MRNA IN ANTIGEN-PRESENTING CELLS Brunhilde Blömeke, University Trier, Trier, Germany

P106. SIGNALING PATHWAYS OF IL-6-MEDIATED DOWNREGULATION OF DRUG DETOXIFICATION CAPACITY IN HUMAN HEPATOCYTES Marcus Klein, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany P107. CYP2E1 HYDROXYLATION OF ANILINE INVOLVES COOPERATIVITY Jessica H. Hartman, Univ of Arkansas for Med Sci, Little Rock, AR, USA P108. CHANGE IN EXPRESSION OF CYTOCHROME P450 IN ULCERATIVE COLITIS AND ANALYSIS OF THE MECHANISM OF CHANGE Yoshiki Kusunoki, Hoshi Univ, Shinagawa-ku, Japan P109. EFFECT OF GENETIC POLYMORPHISM IN CYTOCHROME P450 2A6 ON THE ENANTIOSELECTIVE METABOLISM OF TEGAFUR TO 5-FLUOROURACIL Ikuo Yamamiya, Taiho Pharmaceutical Co. Ltd., Tsukuba, Japan P110. EXPRESSION AND CHARACTERIZATION OF CYNOMOLGUS CYTOCHROME P450 3A4 Murali Subramanian, BBRC, Banalore, India

DIFFERENCES IN METABOLISM (SPECIES, GENDER, AGE, DISEASES) (P111 – P119) P111. COMPARATIVE STUDY OF THE METABOLIC PATHWAY OF NEW ANTHELMINTIC DRUG MONEPANTEL IN HOST AND PARAZITE USING UHPLC/MS TECHNIQUE Lucie Stuchlikova, Faculty of Pharmacy, Charles University in Prague, Hradec Kralove, Czech Republic P112. SPECIES SELECTIVITY IN GLUCURONIDATION KINETICS OF AN MTOR INHIBITOR Yohannes Teffera, Amgen, Cambridge, MA, USA P113. CLOZAPINE BIOACTIVATION AND BIOINACTIVATION IN HUMANS: ROLE OF GST NULL GENOTYPES AS RISK FACTOR FOR IDIOSYNCRATIC DRUG REACTIONS? Sanja Dragovic, Vrije Universiteit Amsterdam, Amsterdam, Netherlands P114. COMPARISON OF ENZYMES AND TRANSPORTERS OF THE TRIPLE KO FRG (FRGN) MOUSE AND THE FRGN MOUSE (MFRGN) REPOPULATED WITH MOUSE HEPATOCYTES: GENE PROFILING AND LIVER PERFUSION STUDIES Edwin C.Y. Chow, University of Toronto, Toronto, ON, Canada P115. GENERATION AND USE OF MULTIPLE CYTOCHROME P450 HUMANIZED AND KNOCKOUT MOUSE MODELS FOR DRUG-DRUG INTERACTION, PHARMACOKINETIC AND SAFETY STUDIES Nico Scheer, TaconicArtemis, Cologne, Germany P116. SPECIES DIFFERENCE OF WARFARIN SENSITIVITY AMONG BIRDS CAN BE EXPLAINED BY THE TWO ENZYMES, CYTOCHROME P450 AND VITAMIN K EPOXIDE REDUCTASE Kensuke P. Watanabe, Hokkaido University, Sapporo, Japan P117. EXPOSURE AND METABOLIC DIFFERENCES AFTER LOXAPINE INHALATION ADMINISTRATION TO MALE AND FEMALE JUVENILE AND ADULT RATS Keith Huie, Alexza Pharmaceuticals Inc, Mountain View, CA, USA P118. METABOLISM OF THE ANTI-HIV DRUG EFAVIRENZ AND PROTEOMIC ANALYSIS OF CYTOCHROME P450 EXPRESSION IN MURINE LIVER AND BRAIN Elisabeth M. Hersman, Johns Hopkins University, School of Medicine, Baltimore, MD, USA

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Poster Details P119. EXPLORING COMPARATIVE PHARMACOKINETICS FOR SCREENING-LEVEL BIOACCUMULATION ASSESSMENT: IN VITRO PHARMACEUTICAL BIOTRANSFORMATION WITH FATHEAD MINNOW (PIMEPHALES PROMELAS) AND RAINBOW TROUT (ONCORHYNCHUS MYKISS) Kristin Connors, Baylor University, Waco, TX, USA

P130. METABOLITE IDENTIFICATION IN DRUG DISCOVERY. NEW TECHNIQUES TO EXPLORE THE HRMS Ismael Zamora, Lead Molecular Design, S.L., San Cugat del Vallés, Spain P131. SIMULTANEOUS PK ANALYSIS AND METABOLITE IDENTIFICATION USING NOVEL MASS SPECTROMETRY ACQUISITION TECHNIQUES James Ferguson, AB SCIEX, Framingham, MA, USA P132. METABOLITE IDENTIFICATION USING DIFFERENTIAL ION MOBILITY SPECTROMETRY COUPLE TO MASS SPECTROMETRY Carmai Seto, AB SCIEX, Concord, ON, Canada P133. THE RELEVANCE OF SOLVENT SELECTION IN METABOLISM STUDIES: ANSAMYCIN DEGRADATION CASE STUDY Sherri Smith, Infinity Pharmaceuticals, Inc., Cambridge, MA, USA P134. BIOACTIVATION STUDIES OF ANTIMYCOBACTERIAL 4-ARYL-2-AMINOTHIAZOLES Mathew Njoroge, University of Cape Town, Cape Town, South Africa P135. IMPROVEMENT IN PREDICTION OF HUMAN PHARMACOKINETICS OF BIOTHERAPEUTICS Yoichi Naritomi, Astellas Pharma. Inc., Tsukuba-shi, Japan P136. PHARMACOKINETICS, DISTRIBUTION, METABOLISM AND EXCRETION OF TEMOZOLOMIDE ESTER, A NEW ALKYLATING AGENT FOR CANCER THEARAPY Jingkai Gu, Jilin University, Changchun, China P137. A NOVEL APPROACH TO AUTOMATED GLUCOSE MONITORING IN AWAKE AND FREELY MOVING ANIMALS Brad Gien, BASi, West Lafayette, IN, USA P138. DESIGN, EVALUATION AND SYNTHESIS OF NOVEL ANTICANCER DRUGS TARGETING THE DIMERIZATION ARM OF EGFR Zechariah Marting, University of Sydney, Sydney, Australia P139. A POTENT MOLECULAR PATHWAY INHIBITOR THAT INHIBITS CANCER CELL PROLIFERATION John Cashman, Human BioMolecular Research Institute, San Diego, CA, USA P140. IN VITRO CHARACTERIZATION OF DP44MT AND BP4ET METABOLIC PRODUCTS Eliska Mackova - Potuckova, Charles University in Prague, Faculty of Pharmacy, Hradec Kralove, Czech Republic P141. NOVEL ZINC PHTHALOCYANINES WITH HIGH ANTITUMOR PHOTODYNAMIC ACTIVITY AND LOW DARK TOXICITY Miloslav Machacek, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic P142. PRECLINICAL METABOLISM AND PHARMACOKINETICS OF BENTYSREPININE (Y101), A NOVEL ANTI-HBV AGENT Huirong Fan, Tianjin Institute of Pharmaceutical Research, Tianjin, China P143. PHARMACOKINETICS, TISSUE DISTRIBUTION, METABOLISM AND EXCRETION OF ONO-8815, A PROSTAGLANDIN E2 RECEPTOR TYPE-2 SELECTIVE AGONIST, IN RATS Tetsu Kondo, Ono Pharmaceutical Co., Ltd., Ibaraki, Japan P144. BILE DUCT-CANNULATED RATS IN MASS BALANCE EXCRETION STUDIES AND METABOLITE PROFILING Helen L. Shen, QPS, LLC, Newark, DE, USA

DISPOSITION (P120 – P125) P120. CONSIDERATIONS TO THE STUDY DESIGN AND INTERPRETATION WHEN CONDUCTING AN INHALED ADME STUDY Colin Webber, Huntingdon Life Sciences, Huntingdon, United Kingdom P121. REGIONAL AND SYSTEMIC DISTRIBUTION OF TEMOZOLOMIDE FROM A POLYMER IMPLANT IN RAT BRAIN Jingkai Gu, Jilin University, Changchun, China P122. DISPOSITION OF PRADIGASTAT (LCQ908) IN HUMANS: IN VIVO AND IN VITRO INVESTIGATIONS Alana Upthagrove, Novartis Institutes for BioMedical Research, East Hanover, NJ, USA P123. THE IMPORTANCE OF VILLOUS PHYSIOLOGY AND MORPHOLOGY IN MECHANISTIC PBPK MODELS Guoying Tai, GlaxoSmithKline, King of Prussia, PA, USA P124. COMPARATIVE IN-VITRO DERMAL PENETRATION STUDIES WITH [14C]-ANILINE USING STRAT-M MEMBRANE AND DERMATOMED HUMAN SKIN Stuart G. Wood, Quotient Bioresearch Limited, Rushden, United Kingdom P125. COMPARISON OF THE DRUG CONCENTRATIONS IN THE BRAIN INTERSTITIAL AND CEREBROSPINAL FLUIDS IN CYNOMOLGUS MONKEYS Yoko Nagaya, Eisai Co., Ltd., Tsukuba, Japan

DNA DAMAGE AND REPAIR (P126) P126. FORMALDEHYDE INFLUENCE DNA DAMAGE REPAIR PROCESS THROUGH PARP-1 PATHWAY IN THE HUMAN BRONCHIAL EPITHELIAL CELL LINES Yuxin Zheng, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China

DRUG DELIVERY (P127 – P128) P127. INVESTIGATING THE ADME PROPERTIES OF AN IONIC LIQUID SALT OF SULFASALZINE, A NOVEL APPROACH TO IMPROVE DRUG EXPOSURE Mohammad Shadid, Takeda Cambridge US, Cambridge, MA, USA P128. SONODYNAMICALLY INDUCED ANTICANCER EFFECTS BY FUNCTIONALIZED FULLERENES Yumiko Iwase, Yokohama College of Pharmacy, Yokohama, Japan

DRUG DISCOVERY AND DEVELOPMENT (P129 – P157) P129. PRE AND POST DERIVATIZATION STABILITY OF MONOAMINES IN RAT BRAIN MICRODIALYSATES IN ABSENCE OF STABILIZING AGENTS Rajesh Kumar Boggavarapu, Suven Life Sciences Ltd, Hyderabad, India

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Poster Details P145. EX VIVO PROTEIN BINDING IN HEALTHY DONORS AND DISEASED PATIENTS, AND COMPARISON OF EX VIVO AND IN VITRO RESULTS Helen L. Shen, QPS, Newark, DE, USA P147. PHARMACOKINETICS OF A NOVEL DGAT1(DIACYLGLYCEROL ACYLTRANSFERASE-1) INHIBITOR, KR-69232 Eun-Young Kwak, Korea Research Institute of Chemical Technology, Daejon, South Korea P148. EPOXYEICOSATRIENOIC ACIDS PREVENT CISPLATIN-INDUCED RENAL APOPTOSIS THROUGH A P38 MAPK REGULATED INTRINSIC MITOCHONDRIAL PATHWAY Yingmei Liu, University of California San Francisco, San Francisco, CA, USA P149. IN VIVO DISCOVERY ADME PROPERTIES OF 10 LATE STAGE IRREVERSIBLE INHIBITORS: CAN TRADITIONAL ADME ASSAYS SERVE AS SCREENING GATES? Ashutosh Kulkarni, Celgene Corporation, San Diego, CA, USA P150. IN VITRO DISCOVERY ADME PROPERTIES OF 10 LATE STAGE IRREVERSIBLE INHIBITORS: CAN TRADITIONAL ADME ASSAYS SERVE AS SCREENING GATES? Ashutosh Kulkarni, Celgene Corporation, San Diego, CA, USA P151. AUTOMATED MULTIPLE CHARGE STATE DETECTION OF PHASE II GLUTATHIONE CONJUGATES FROM HRMS QTOF DATA Mark D. Wrona, Waters Corporation, Milford, MA, USA P152. CHARACTERIZATION OF THE ABSORPTION, METABOLISM, AND EXCRETION OF GDC-0068, AN ATPCOMPETITIVE AKT INHIBITOR, FOLLOWING SINGLE ORAL ADMINISTRATION TO CYNOMOLGUS MONKEYS Bianca M. Liederer, Genentech Inc., South San Francisco, CA, USA P153. SYSTEMIC EXPOSURE TO THE METABOLITES OF LESOGABERAN IN HUMANS AND ANIMALS- A CASE STUDY OF METABOLITES IN SAFETY TESTING Ann Aurell Holmberg, AstraZeneca, Mölndal, Sweden P154. PREDICTION OF HUMAN PHARMACOKINETICS OF EPITINIB FROM PRECLINICAL PHARMACOKINETICS BY A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL Yang Sai, Hutchison MediPharma Limited, Shanghai, China P155. OPTIMIZATION AND QUALIFICATION OF ULTRACENTRIFUGATION FOR PROTEIN BINDING DETERMINATION Helen L. Shen, QPS, LLC, Newark, DE, USA P156. NEURO-PHARMACOKINETICS BASED PREDICTION OF P-GLYCOPROTEIN LIABILITY IN EARLY DRUG DISCOVERY Nageswara Rao Muddana, Suven Life Sciences Ltd, Hyderabad, India P157. FINE ISOTOPIC PATTERN RECOGNITION FOR SMALL MOLECULE IDENTIFICATION Caroline Ding, Thermo Fisher Scientific, San Jose, CA, USA

P159. TIME-DEPENDENT BALANCE BETWEEN INDUCING AND INHIBITING EFFECTS OF P-GLYCOPROTEIN AND CYTOCHROME P450 3A Keizo Fukushima, Kobe Gakuin University, Kobe, Japan P160. USE OF NATURAL AND SYNTHETIC CANNABINOIDS TO ESTABLISH CANNABINOID RECEPTORS AS NOVEL TARGETS FOR THE TREATMENT OF BREAST CANCER Centdrika Dates, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA P161. CRIZOTINIB MODULATES ACTIVITIES AND EXPRESSIONS OF CYPS 2B6, 2C9 AND 3A4/5 IN HUMAN HEPATOCYTES Kan He, Biotranex, Monmouth Junction, NJ, USA P162. MECHANISM-BASED INACTIVATION OF CYTOCHROME P450 2D6 BY BERBERINE ISOLATED FROM COPTIS JAPONICA Min-Jung Kim, Inje Univ Col of Med, Busanjin-gu, South Korea P163. COMPARISON OF THE IC50-SHIFT AND % INHIBITION ASSAY TO EVALUATE TIME-DEPENDENT INHIBITION Mey Y. Lee, Amgen, South San Francisco, CA, USA P164. EFFECTS OF METRONIDAZOLE ON THE HEPATIC CYP ACTIVITY AND EXPRESSION Toshiyuki Kudo, Musashino Univ, Tokyo, Japan P165. NAMPT INHIBITOR GNE-618 DDI RISK ASSESSMENT: PUTTING IN VITRO DATA INTO PERSPECTIVE Bianca M. Liederer, Genentech Inc., South San Francisco, CA, USA P166. DRUG INTERACTION STUDIES DURING DRUG DEVELOPMENT: CURRENT STATUS AND REGULATORY PERSPECTIVES IN JAPAN Masanobu Sato, Pharmaceuticals and Medical Devices Agency (PMDA), Tokyo, Japan P167. NEW JAPANESE DRAFT GUIDANCE ON DRUG INTERACTION STUDIES AND LABELING RECOMMENDATIONS Naomi Nagai, The MHLW Drug Interaction Working Group and Pharmaceuticals and Medical Devices Agency (PMDA), Tokyo, Japan P168. ANALYSIS OF METABOLISM AND TRANSPORT DRUG INTERACTION DATA IN 2012 NEW DRUG APPLICATIONS Isabelle Ragueneau-Majlessi, University of Washington, Seattle, WA, USA P169. ASSESSMENT OF POTENTIAL CYTOCHROME P450S DRUG-DRUG INTERACTIONS USING STATIC AND DYNAMIC MODELS FOR ML-1 Lawrence H. Cohen, Millennium Pharmaceuticals, Cambridge, MA, USA P170. PACLITAXEL ENHANCES CELLULAR UPTAKE OF GEMCITABINE THROUGH UP-REGULATION OF NUCLEOSIDE TRANSPORTERS CNT1 AND CNT3 Zeen Tong, Celgene Corporation, Summit, NJ, USA P171. APPLICATION OF UPCYTE® HUMAN HEPATOCYTES TO CYP INHIBITION AND INDUCTION SCREENING Nicola J. Hewitt, Medicyte GmbH, Heidelberg, Germany P172. INHIBITION MECHANISM STUDY FOR HWANG-RYUNHAE-DOK-TANG ON CYTOCHROME P450 IN HUMAN LIVER MICROSOMES Soo Jin Oh, Korea Research Institute of Bioscience and Biotechnology, Ochang, South Korea

DRUG INTERACTION (P158 – P175) P158. EVALUATION OF PHARMACOKINETIC INTERACTION BETWEEN FIMASARTAN AND HYDROCHLOROTHIAZIDE IN RATS Soo Heui Paik, Boryung Pharm. Co. Ltd., Ansan, South Korea

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Poster Details P173. CHEMOSYNTHETIC LIVERS: EVALUATING PLAUSIBLE DRUG-DRUG INTERACTIONS RELATING TO METABOLITE SUPPRESSION OR ATTENUATION Mukund S. Chorghade, Empiriko Corporation, Newton, MA, USA P174. LONG-LASTING INHIBITION OF INTESTINAL ABSORPTIVE TRANSPORTER OATP2B1 BY FRUIT JUICE Yukiko Murata, Kanazawa University, Kanazawa, Japan P175. DRUG-DRUG INTERACTION SIMULATIONS OF TIMEDEPENDENT CYP2C19 INHIBITION ON OMEPRAZOLE AND PROGESTERONE FROM IN VITRO METABOLISM DATA USING SIMCYP SIMULATOR Jinrong Liu, Abbott laboratories, Abbott Park, IL, USA

P186. TIME-COURSE OF CYTOCHROME P450 (CYP450) INDUCTION IN CULTURED HUMAN HEPATOCYTES: EVALUATION OF ACTIVITY AND MRNA EXPRESSION PROFILES FOR SIX INDUCIBLE CYP450 ENZYMES David B. Buckley, XenoTech, LLC, Lenexa, KS, USA P187. TRANSCRIPT REGULATION OF 42 ADME GENES BY PROTOTYPICAL INDUCERS IN HUMAN HEPATOCYTES Timothy Moeller, Celsis In Vitro Technologies, Baltimore, MD, USA P188. TRACING CYP INDUCTION: A NOVEL APPROACH TO MEET FDA RECOMMENDATIONS ON DRUG-DRUG INTERACTIONS Hinnerk Boriss, Sovicell GmbH, Leipzig, Germany P189. PREDICTION OF CLINICAL CYP3A4 INDUCTION USING POOLED HUMAN HEPATOCYTES ON CELL ARRAY 3DCULTURE PLATE FOR DRUG-METABOLIZING ENZYME INDUCTION STUDIES IN DRUG DISCOVERY Jiro Kuze, Taiho pharmaceutical co., ltd, Tsukuba, Japan

ENVIRONMENTAL TOXICOLOGY (P176 – P183) P176. XENOBIOTIC DETOXIFICATION FROM AN ENVIRONMENTAL PERSPECTIVE: THE ROLES OF MICROBIAL ARYLAMINE N-ACETYLTRANSFERASES Sotiria Boukouvala, Democritus University of Thrace, Alexandroupolis, Greece P177. PROTECTION AGAINST SODIUM ARSENITE – INDUCED TOXICITY IN RATS BY NONI EXTRACT (MORINDA CITRIFOLIA LINN.) Olufunke E. Ola-Davies, University of Ibadan, Ibadan, Nigeria P178. HEPATIC GENE EXPRESSION PROFILES FROM RATS EXPOSED IN UTERO AND/OR THROUGH LACTATION TO MIXTURES OF ENVIRONMENTAL CONTAMINANTS Cathy Cummings-Lorbetskie, Health Canada, Ottawa, ON, Canada P179. DEVELOPMENTAL EFFECTS OF MALATHION EXPOSURE ON LOCOMOTOR AND EXPLORATORY ACTIVITIES IN WISTAR RAT Pacôme Kouadio N'Go, Unit of Clinic and Cognitive Neuroscience and Health, Faculty of Sciences, Kenitra, Morocco P180. EVIDENCE OF ELEVATED PHTHALATE ESTER LEVELS IN FIN AND SHELL FISH FROM EPE AND LAGOS LAGOON, NIGERIA Aina O. Adeogun, University of Ibadan, Ibadan, Nigeria P181. FUNCTIONAL IMPAIRMENT OF MUSCLE GLYCOGEN PHOSPHORYLASE BY MERCURY Ximing Xu, Univ Paris Diderot, Paris, France P182. FIRST EVIDENCE OF ENDOCRINE DISRUPTION IN TILAPIAS FROM OGUN RIVER, NIGERIA Oju R. Ibor, University of Ibadan, Ibadan, Nigeria P183. SPERMATOZOA MORPHOLOGY AND CHARACTERISTICS OF SPONDIA MOMBIN.L.(ANACARDIACEAE) PROTECTED MALE WISTAR RATS EXPOSED TO SODIUM ARSENITE Olumide S. Ajani, UNIVERSITY OF IBADAN, Ibadan, Nigeria

ENZYME INHIBITION/INACTIVATION (P190 – P205) P190. ESOMEPRAZOLE MODIFIES HEME IN HUMAN LIVER MICROSOMES: PRELIMINARY HIGH-RESOLUTION MASS SPECTROMETRIC EVIDENCE FOR THE MECHANISM OF INACTIVATION OF CYTOCHROME P450 Andrew Parkinson, XPD Consulting, Shawnee, KS, USA P191. POTENT INHIBITION OF HUMAN SULT1E1 BY TRICLOSAN Katie Jo Rohn-Glowacki, University of Alabama at Birmingham, Birmingham, AL, USA P192. ENZYME-SPECIFIC INHIBITION OF HUMAN GLUTATHIONE TRANSFERASES BY NAPHTHALENE ANALOGUES OF 1-CHLORO-2,4-DINITROBENZENE Hilary Groom, University of Guelph, Guelph, ON, Canada P193. INDUCTION POTENCY AND INHIBITORY EFFECT OF A NOVEL DEOXYURIDINE TRIPHOSPHATASE INHIBITOR, TAS114, ON DRUG-METABOLIZING ENZYMES IN HUMANS: IN VITRO AND IN VIVO STUDIES Kunihiro Yoshisue, Taiho Pharmaceutical Co. Ltd., Tokushima, Japan P194. EVALUATION OF TIME-DEPENDENT INHIBITION OF CYP3A4 IN PLATED AND SUSPENDEND HUMAN HEPATOCYTES BY MODEL INHIBITORS J. George Zhang, Corning Life Sciences, Woburn, MA, USA P195. EVALUATION OF SANDWICH CULTURED HUMAN HEPATOCYTES (SCHH) AS AN IN VITRO MODEL TO ASSESS TIME DEPENDENT INHIBITION (TDI) OF CYTOCHROME P450 3A4 Aneesh Arvind Argikar, Temple University, Philadelphia, PA, USA P196. RELATIONSHIP OF PASSIVE PERMEABILITY AND CYTOCHROME P450 (CYP) 3A4 INHIBITION Ling Li, Lexicon Pharmaceuticals Inc, The Woodlands, TX, USA P197. DEVELOPMENT AND VALIDATION OF AN IN VITRO, SEVEN-IN-ONE CYTOCHROME P450 ASSAY FOR EVALUATION OF BOTH DIRECT AND TIME-DEPENDENT INHIBITION Uwe Fuhr, University of Cologne, Cologne, Germany

ENZYME BIO-ENGINEERING (P184) P184. A NOVEL CANCER SUICIDE GENE THERAPY COMBINING THE IMPROVEMENT OF CYCLOPHOSPHAMIDE TUMOR CYTOTOXICITY AND THE DEVELOPMENT OF AN ANTI-TUMOR IMMUNE RESPONSE Walid Touati, INSERM U775, Paris, France

ENZYME INDUCTION (P185 – P189) P185. EVALUATION OF “R3” AND RELATIVE INDUCTION SCORES (RIS) DERIVED FROM ENZYME ACTIVITY AS PREDICTORS OF CYP3A4 INDUCTION RESPONSE IN VIVO J. George Zhang, Corning Life Sciences, Woburn, MA, USA

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Poster Details P198. AUTOMATED UPLC-MS/MS ASSAYS FOR REGULATORY-COMPLIANT ASSESSMENT OF REVERSIBLE AND METABOLISM DEPENDENT INHIBITION OF HUMAN CYP ENZYMES David Wilkinson, Covance Laboratories Ltd, Harrogate, United Kingdom P199. HUMAN HEPATOCYTE BASED CYP3A4 INHIBITION IC50-SHIFT ASSAY – PREDICTION OF CLINICAL DRUGDRUG INTERACTIONS Jacob A. Olsen, Sanofi, Frankfurt am Main, Germany P200. A COMPARISON BETWEEN A NEW BRONCHODILATOR CONTAINING A THIOPHENE RING AND TIENILIC ACID, IN AN IN VITRO STUDY OF MECHANISMBASED INACTIVATION OF CYP450 Michela Salvadori, Chiesi Farmaceutici, Parma, Italy P201. SUBSTRATE-SPECIFIC INACTIVATION OF CYP3A BY THE HIV PROTEASE INHIBITORS RITONAVIR, SAQUINAVIR AND AMPRENAVIR Faraz Kazmi, XenoTech, LLC, Lenexa, KS, USA P202. COMPARISON OF INHIBITION OF CYP1A2, 2C9 AND 3A4 USING HUMAN LIVER MICROSOMES AND HEPATOCYTES Timothy A. Moeller, Celsis In Vitro Technologies, Baltimore, MD, USA P203. VARIATION IN THE IN VITRO INHIBITION OF CYP3A4, CYP2D6 AND CYP1A2 BY DIFFERENT COMMERCIAL RHODIOLA ROSEA PRODUCTS Ole Kristian F. Thu, Norwegian University of Science and Technology, Trondheim, Norway P204. GOSSYPOL EXHIBITS POTENT INHIBITORY EFFECTS TO HUMAN CARBOXYLESTERASES Guang-Bo Ge, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China P205. USE OF THE CYP3A4 SELECTIVE INHIBITOR CYP3CIDE IN CYP3A5 GENOTYPED CRYOPRESERVED HUMAN HEPATOCYTES TO EXPLORE THE INDIVIDUAL CONTRIBUTION OF CYP3A4 AND CYP3A5 IN DRUG METABOLISM Scott Heyward, Celsis In Vitro Technologies, Baltimore, MD, USA

P210. ENERGY SENSING COACTIVATOR PGC-1 REGULATES NOVEL MOUSE HEPATIC CYP GENES INCLUDING VITAMIN D METABOLIZING CYP24A1 AND CYP2R1 S.M. Aatsinki, University of Oulu, Oulu, Finland P211. ROLE OF ER STRESS AND PPARALPHA IN THE REGULATION OF CYP3A4 BY FGF21 IN A MODEL OF NONALCOHOLIC FATTY LIVER DISEASE Sarah J. Woolsey, The University of Western Ontario, London, ON, Canada P212. ENHANCED SENSITIVITY OF LDMM-STABILIZED HUMAN HEPATOCYTES TOWARDS CYTOKINE-INDUCED DOWN REGULATION OF GENE EXPRESSION OF P450 ISOFORMS, UPTAKE TRANSPORTERS AND EFFLUX TRANSPORTERS Qian Yang, In Vitro ADMET Laboratories LLC, Columbia, MD, USA P213. DOWN-REGULATION OF MOUSE HEPATIC CYTOCHROME P450 3A PROTEIN BY 3METHYLCHOLANTHRENE DOES NOT REQUIRE CYTOCHROME P450-DEPENDENT METABOLISM David S. Riddick, University of Toronto, Toronto, ON, Canada P214. GLUCOCORTICOID INDUCTION OF THE ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR IN RAT LIVER Sarah R. Hunter, University of Toronto, Toronto, ON, Canada P215. DUAL ROLES OF NUCLEAR RECEPTOR LXRΑ IN THE CYP3A4 EXPRESSION IN HUMAN HEPATOCYTES AS A POSITIVE AND NEGATIVE REGULATOR Kouichi Yoshinari, Gradueate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan P216. RNA-SEQ REVEALS TRANSCRIPTIONAL RESPONSE OF CODING RNAS AND LONG NON-CODING RNAS TO RIFAMPICIN TREATMENT IN PRIMARY HUMAN HEPATOCYTES AND HEPARG CELLS Chad Pope, University of Connecticut, Storrs, CT, USA P217. INDUCTION OF RAT HEPATIC NADPH-CYTOCHROME P450 OXIDOREDUCTASE BY DEXAMETHASONE: ARE MULTIPLE RECEPTORS INVOLVED? Alex Vonk, University of Toronto, Toronto, ON, Canada P218. GSK3Β INHIBITORS REGULATE CYP EXPRESSION IN PRIMARY HUMAN HEPATOCYTES BY MANY WAYS: ACTIVATION OF CTNNB1, AHR AND PXR Sabine Gerbal-Chaloin, INSERM U1040, Montpellier, France P219. EXPRESSION OF PH REGULATORY PROTEINS MAY INFLUENCE DRUG RESISTANCE Lukas Klameth, Ludwig Boltzmann Cluster Translational Oncology, Vienna, Austria P220. 1-BROMOPROPANE INCREASES THE EXPRESSION OF PROINFLAMMATORY CYTOKINES AND SECRETION OF BETA-HEXOSAMINIDASE IN RBL-2H3 CELLS Hwa Jeong Han, Chungnam National University, Daejeon, South Korea P221. EXPRESSION OF POORLY CHARACTERIZED MEMBERS OF SDR SUPERFAMILY IN HUMAN TISSUES Beata Malcekova, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic P222. DISTAL PROMOTER REGIONS OF HUMAN OROSOMUCOID 1 AND 2 GENES DIFFERENTIALLY REGULATE THEIR GENE EXPRESSIONS AND ACUTE PHASE RESPONSES Yoshiro Saito, National Institute of Health Sciences, Tokyo, Japan

EXTRAHEPATIC METABOLISM (P206 – P208) P206. SKIN METABOLISM OF PRO OR PRE HAPTENS: ITS ROLE IN ALLERGIC CONTACT DERMATITIS Joan Eilstein, L'Oreal Research and Innovation - Advanced Research, Aulnay sous Bois, France P207. METABOILSM AND ELIMINATION OF GYRAR COMPOUND, AZ1419; CONTRIBUTION OF GUT BACTERIA Karthick Vishwanathan, AstraZeneca Pharmaceuticals, Waltham, MA, USA P208. FMO1-MEDIATED COPE ELIMINATION IN THE METABOLISM OF E7016 IN HUMAN KIDNEY S9 Y. Amy Siu, Eisai Inc, Andover, MA, USA

GENE EXPRESSION AND REGULATION (P209 – P225) P209. REGULATION OF REDOX-DEPENDENT GENE EXPRESSION UNDER OF DRUG RESISTANCE OF CANCER CELLS Elena Kalinina, Peoples' Friendship University of Russia, Moscow, Russia

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Poster Details P223. PXR IS A LIGAND-ACTIVATED SIGNAL SCAFFOLD THAT FACILITATES PP2C DEPHOSPHORYLATING SGK2 TO REGULATE HEPATIC GLUCONEOGENESIS Saki Gotoh, National Institute of Environmental Health Sciences/National Institute of Health, Research Triangle Park, NC, USA P224. ENDOTOXIN UP-REGULATES THE PROINFLAMMATORY CYTOKINES TNF-A AND IL-6 IN FRESHLY-ISOLATED HUMAN KUPFFER CELLS David B. Buckley, XenoTech, LLC, Lenexa, KS, USA P225. INDUCTION OF UBCM4 BY AHR RESULTS IN C-FOS DEGRADATION Alejandro Mejia-Garcia, CINVESTEV-IPN, Mexico, Mexico

HERBAL MEDICINE-ACTIVE COMPOUNDS (P236 – P239) P236. TRPC6-ACTIVATING PHLOROGLUCINOL DERIVATIVES OF HYPERFORIN LACK PXR-ACTIVATION AND INDUCTION OF ADME GENE EXPRESSION IN HUMAN HEPATOCYTES Benjamin A. Kandel, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany P237. MODULATION OF SELECTED ANTIOXIDANT ENZYMES BY CRANBERRIES AND GREEN TEA POLYPHENOLS IN MICE Hana Bartikova, Faculty of Pharmacy, Charles University in Prague, Hradec Kralove, Czech Republic P238. INDUCTION OF ANTIOXIDANT/DETOXIFYING SYSTEM IN PRIMARY RAT HEPATOCYTES BY LISOSAN G, A FERMENTED POWDER OF WHEAT Vincenzo Longo, Institute of Agricultural Biology and Biotechnology UOS-IBBA, CNR, Pisa, Pisa, Italy P239. GLAUCARUBULONE GLUCOPYRANOSIDE, A NATURAL QUASSINOID INHIBITS PRO-CARCINOGEN BIOACTIVATING CYP ENZYMES IN VITRO AND DISPLAYS POTENT IMPACT ON BREAST CANCER CELL PROLIFERATION Rupika Delgoda, Univ. of the West Indies, Mona, Jamaica

GENOMICS/METABOLOMICS/PROTEOMICS (P226 – P229) P226. EXPOSURE ASSESSMENT OF PESTICIDES AND XENOBIOTICS IN SPOT URINE COLLECTIONS Tauri Senn, University of Washington, Seattle, WA, USA P227. ABSTRACT WITHDRAWN P228. INVESTIGATION OF HOST-GUT MICROBIOME INTERACTION IN TACRINE-DOSED LISTER-HOODED RATS THROUGH FECAL METABOLIC PROFILING Lian Yee Yip, National University of Singapore, Singapore, Singapore P229. ABSOLUTE QUANTIFICATION OF TRANSPORTER PROTEINS ALONG THE INTESTINAL TRACT OF PIGS Evita van de Steeg, TNO, Zeist, Netherlands

HERB-DRUG INTERACTIONS (P240 – P245) P240. PRE-CLINICAL EVIDENCE OF LIFE-THREATENING PHARMACOKINETIC INTERACTION BETWEEN QUERCETIN AND METHOTREXATE Prashant B. Musmade, Manipal College of Pharmaceutical Sciences, Manipal, India P241. IMPACT OF ALOE VERA JUICE ON IN VITRO P-GP TRANSPORT AND CYP3A4 METABOLISM Ane Djuv, Norwegian University of Science and Technology, Trondheim, Norway P242. PK/PD EVALUATION OF METABOLISM-BASED SYNERGY: A CLASSICAL HERB PAIR RADIX ANGELICAE DAHURICAE AND RHIZOME LIGUSTICI Xin He, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China P243. INHIBITORY EFFECTS OF AN AQUEOUS EXTRACT OF CURCUMA XANTHORRHIZA AND ITS CONSTITUENTS ON CYP450 ISOFORMS Sabariah Ismail, Universiti Sains Malaysia, Pulau Pinang, Malaysia P244. IN VITRO CYP3A4 INHIBITION BY FRACTIONATED RHODIOLA ROSEA EXTRACTS Bent H. Hellum, Norwegian University of Science and Technology, Trondheim, Norway P245. STUDIES ON LIGNUM DALLBERGIAE ODORIFERAE ASSIST RADIX SALVIAE MILTIORRHIZAE BY OVERLAPPING REGULATION OF P-GP/CYP3A VIA PXR NUCLEAR RECEPTOR PATHWAY Zhihong Yang, Institute of Medicinal Plant Development, Beijing, China

HEPATOCYTES (P230 – P235) P230. USE OF HIGH RESOLUTION ACCURATE MASS SPECTROMETRY WITH AN EXOGENOUS MIXTURE OF GSH AND STABLE ISOTOPE-LABELED GSH TO TRAP REACTIVE METABOLITES OF TROGLITAZONE IN HUMAN HEPATOCYTES Igor Mezine, Absorption Systems, Exton, PA, USA P231. CULTURED HUMAN HEPATOCYTES AS A MODEL FOR EVALUATION OF POTENTIAL SUBSTRATES OF ALDEHYDE OXIDASE: EFFECTS ON METABOLIC CLEARANCE OF DISCOVERY COMPOUNDS Mary Grubb, Bristol-Myers Squibb Co, Princeton, NJ, USA P232. CHARACTERIZATION OF THE HEPATIC TRANSPORT AND DISPOSITION OF GEMFIBROZIL AND ITS METABOLITE Emi Kimoto, Pfizer Inc., Groton, CT, USA P233. BIOACTIVATION AND TOXICITY OF ACETAMINOPHEN IN RAT PRIMARY HEPATOCYTES CULTURED IN MICROPATTERNED CO-CULTURES Okechukwu Ukairo, Hepregen Corporation, Medford, MA, USA P234. FUNCTIONS AND GENE EXPRESSIONS OF SANDWICH CULTURED-PRIMARY RAT HEPATOCYTES ON OXYGENPERMEABLE MEMBRANES UNDER PHYSIOLOGICAL OXYGEN CONCENTRATIONS Wenjin Xiao, Institue of Industrial Science, The University of Tokyo, Tokyo, Japan P235. ROLE OF MIRNAS IN DIFFERENTIATION OF HEPATOCYTES AND APPLICATION TO STEM CELL DERIVED HEPATOCYTE PROTOCOLS Jenna Voellinger, University of Washington, Seattle, WA, USA

HIGH THROUGHPUT TECHNIQUES (P246 – P250) P246. DEVELOPMENT OF A MINIATURIZED MECHANISMBASED INHIBITION ASSAY FOR HIGH-THROUGHPUT MASS SPECTROMETRY ANALYSIS Jing Wang, Labcyte, Inc., Sunnyvale, CA, USA

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Poster Details P247. STATE OF THE ART IN VITRO ADME ASSAYS AND WORK FLOW IN PHARMACEUTICAL DISCOVERY Yau Yi Lau, Abbvie Inc, North Chicago, IL, USA P248. ULTRAFAST PLASMA PROTEIN BINDING ANALYSIS USING A HIGH-THROUGHPUT SPE/TOF-MS SYSTEM Kari E. Schlicht, Agilent Technologies, Wakefield, MA, USA P249. A HIGH THROUGHPUT ASSAY FOR ISOFORMSPECIFIC P450 INHIBITION IN HUMAN HEPATOCYTES Albert P. Li, In Vitro ADMET Laboratories LLC, Columbia, MD, USA P250. TOXICITY OF THE DIARRHETIC MARINE PHYCOTOXINS OKADAIC ACID AND ITS ANALOGUES DINOPHYSISTOXIN-1 AND -2 IN THE HUMAN HEPATIC HEPARG CELL LINE Pierre-Jean Ferron, ANSES, Fougères, France

P260. MATHEMATICAL MODELING OF IN VITRO HEPATIC DISPOSITION OF MYCOPHENOLIC ACID AND ITS GLUCURONIDE IN SANDWICH-CULTURED HUMAN HEPATOCYTES Norikazu Matsunaga, Kanazawa University, Kanazawa, Japan P261. SUBSTRATES-DEPENDENT INFLUENCE ON PROBING METABOLIZING ENZYME-MEDIATED DRUG INTERACTIONS POTENTIALS IN VIVO Ling Yang, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China P262. ESTIMATION OF IN VIVO SKIN AND SYSTEMIC EXPOSURE FOR AROMATIC AMINE HAIR DYES: EXTRAPOLATION FROM KERATINOCYTE AND HEPATOCYTE METABOLISM KINETICS IN VITRO John D. Manwaring, Procter & Gamble Co., Mason, OH, USA P263. APPLICATION OF IN VITRO-IN VIVO EXTRAPOLATION (IVIVE) TO INVESTIGATE THE RATE-DETERMINING STEPS IN THE HEPATIC CLEARANCE OF HIV PROTEASE INHIBITORS IN RAT Tom De Bruyn, KU Leuven, Leuven, Belgium P264. TRANSLATIONAL PBPK MODELING AND SIMULATION OF THE HEPATIC DISPOSITION OF ACTIVELY TRANSPORTED DRUGS BASED ON INDIVIDUAL TRANSPORTER ASSAYS Evita van de Steeg, TNO, Zeist, Netherlands

IN SILICO (P251 – P256) P251. PREDICTION OF PLASMA PROTEIN BINDING USING GENETIC ALGORITHMS AND LOCAL LAZY REGRESSIONS Sitarama Gunturi, Tata Consultancy Services Ltd.,, Hyderabad, India P252. A MECHANISM BASED MODEL OF STEROIDS METABOLIC SITES PREDICTION FOR CYTOCHROME P450 3A4 Ling Yang, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, DaLian, China P253. COMPUTATIONAL INSIGHT INTO SUBSTRATE BINDING DETERMINANTS OF CYTOCHROME P450 2A6 Ling Yang, Dalian Institute of Chemical Physics, Dalian, China P254. DYNAMIC MODELLING OF HEPATOCYTE REGULATORY NETWORKS USING NOVEL PETRI NETLINKED FLUX BALANCE ANALYSIS Nick J. Plant, University of Surrey, Guildford, United Kingdom P255. SIMULATING THE EFFECT OF UGT, SULT AND MRP2 INDUCTION AND/OR INHIBITION ON THE DISPOSITION OF RESVERATROL AND ITS CONJUGATED METABOLITES Aneesh Arvind Argikar, Temple University, Philadelphia, PA, USA P256. EXAMINING THE RELATIVE ROLES OF APICAL VERSUS BASOLATERAL TRANSPORT IN DETERMINING DRUG FATE Nick J. Plant, University of Surrey, Guildford, United Kingdom

IN VITRO TECHNIQUES (P265 – P273) P265. CHARACTERIZATION OF HUMAN COLONIC CARCINOMA CELL LINES FOR STUDYING INTESTINAL PERMEABILITY AND FIRST-PASS METABOLISM AS AN ALTERNATIVE TO CACO-2 CELLS Yoshiyuki Yamaura, University of Washington, Seattle, WA, USA P266. IN VITRO INVESTIGATION OF BILE RELEASE DYNAMICS OF PRIMARY HUMAN HEPATOCYTES AND HEPARG CELLS Marc Lübberstedt, Charité University Medicine Berlin, Berlin, Germany P267. EVALUATION OF TRANSIL HIGH SENSITIVITY BINDING ASSAY FOR HIGHLY PLASMA PROTEIN BOUND COMPOUNDS Heather Eng, Pfizer Global Research and Development, Groton, CT, USA P268. AN IN VITRO SCREENING METHOD TO EVALUATE THE DRUG-DRUG INTERACTION DUE TO INHIBITION OF SULFOTRANSFERASE ENZYMES (SULTS) Mohammed Taimi, Cyprotex, Watertown, MA, USA P269. A HUMAN IN VITRO MODEL FOR THE INVESTIGATION OF INFLAMMATORY REACTIONS IN XENOBIOTIC MEDIATED HEPATOTOXICITY Georg Damm, Charité University Medicine Berlin, Berlin, Germany P270. IN VITRO METABOLISM STUDY OF DESIGNER DRUGS USING A HEPATOCYTE SPHEROID ARRAY KIT Tatsuyuki Kanamori, National Research Institute of Police Science, Kashiwa, Japan P271. PERMEABILITY OF PIPERINE ACROSS MDCK CELL MONOLAYERS COMPARED WITH IN SILICO PREDICTION BY USING ADMET PREDICTOR™ SOFTWARE Chatsiri Jesadakultavee, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand

IN VITRO / IN VIVO EXTRAPOLATION (P257 – P264) P257. MIDAZOLAM CLEARANCE IN HUMAN HEPATOCYTES IS RESTRICTED COMPARED WITH HUMAN LIVER MICROSOMES BUT NOT BY CELL PERMEABILITY OR COFACTOR AVAILABILITY Faraz Kazmi, XenoTech, LLC, Lenexa, KS, USA P258. TEST SYSTEM-DEPENDENT CLEARANCE OF CYP2D6 AND CYP3A4/5 SUBSTRATES: A COMPARISON OF HUMAN LIVER MICROSOMES AND CRYOPRESERVED HUMAN HEPATOCYTES Faraz Kazmi, XenoTech, LLC, Lenexa, KS, USA P259. PREDICTION OF UGT-MEDIATED GEMFIBROZIL CLEARANCE USING IN VITRO DETERMINED INTRINSIC CLEARANCE Anil Kolur, Eli Lilly & Company, Indianapolis, IN, USA

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Poster Details P272. USE OF DEXTRAN-COATED CHARCOAL METHOD FOR MEASURING THE RATE OF DISSOCIATION (KOFF) OF SMALL MOLECULES FROM PLASMA PROTEINS Kamelia Behnia, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA P273. DEVELOPMENT OF A LC/MS/MS SCREENING METHOD TO EVALUATE THE IMPACT OF DRUGS ON CORTISOL BIOSYNTHESIS IN VITRO Mohammed Taimi, Cyprotex, Watertown, MA, USA

P285. POTENTIAL MOLECULAR CYTOTOXIC MECHANISMS OF METHOTREXATE IN ISOLATED RAT HEPATOCYTES Abdullah Al Maruf, University of Toronto, Toronto, ON, Canada P286. INVESTIGATION OF ISONIAZID DILI MECHANISMS IN HUMAN INDUCED PLURIPOTENT STEM CELL DERIVED HEPATOCYTES Jingtao Lu, The Hamner Institutes for Health Sciences, Reseach Triangle Park, NC, USA P287. THE ANTI-HIV DRUG EFAVIRENZ INCREASES THE PROTEIN EXPRESSION AND ACTIVITY OF IRE1Α IN PRIMARY HUMAN HEPATOCYTES Jennifer VanAusdall, Johns Hopkins University School of Medicine, Baltimore, MD, USA P288. INTESTINAL ABSORPTION OF PYRROLIZIDINE ALKALOIDS AND THEIR N-OXIDES Mengbi Yang, The Chinese University of Hong Kong, Hong Kong, Hong Kong P289. INCREASED DNA METHYLATION OF SCAVENGER RECEPTOR CLASS B TYPE I MEDIATE INHIBITORY EFFECT OF PRENATAL CAFFEINE INGESTION ON FETAL ADRENAL CHOLESTEROL UPTAKE Jie Ping, Medical School of Wuhan University, Wuhan, China P290. THE INVOLVEMENT OF THE NEUTROPHIL OXIDATIVE BURST PATHWAY IN THE COVALENT BINDING OF AMODIAQUINE TO RODENT NEUTROPHILS IN VIVO: IMPLICATIONS FOR DRUG-INDUCED AGRANULOCYTOSIS Alexandra R. Lobach, University of Toronto, Toronto, ON, Canada P291. PHARMACOKINETICS OF ORAL DICHLOROACETATE IN DOGS Peter W. Stacpoole, University of Florida, Gainesville, FL, USA

MECHANISMS OF XENOBIOTIC TOXICITIES (P274 – P291) P274. INVESTIGATION OF AMINOGLUTETHIMIDE-INDUCED CHANGES IN NEUTROPHILS: IMPLICATIONS FOR IDIOSYNCRATIC DRUG-INDUCED AGRANULOCYTOSIS Winnie Ng, University of Toronto, Toronto, ON, Canada P275. MECHANISTIC AND EPIDEMIOLOGIC INSIGHTS INTO UPREGULATION OF GENE OF INFLUENZA VIRUS NS1 PROTEIN BY DIOXIN IN HOST CELL Ilya B. Tsyrlov, XENOTOX, Inc., Scarsdale, NY, USA P276. A PREVIOUSLY UNEXPLORED LINK BETWEEN CANNABINOID RECEPTORS AND UDPGLUCURONOSYLTRANSFERASES IN CANCER Anna Radominska-Pandya, University of Arkansas for Medical Sciences, Little Rock, AR, USA P277. TRANSCRIPTOMIC AND METABONOMIC EFFECTS OF TAMOXIFEN METABOLIZATION BY CYP3A4 AND CYP2D6 IN HEPG2 CELLS Aurelie J. Krol, INSERM U775, Paris, France P278. COVALENT INTERACTION OF AN IMINIUM ION METABOLITE OF RIMONABANT WITH BIOLOGICAL TARGETS Annika Thorsell, AstraZeneca, Mölndal, Sweden P279. DETECTION OF XENOBIOTIC-INDUCED HEPATOTOXICITY IN HUMAN IPSC-DERIVED HEPATOCYTES Shannon Einhorn, Cellular Dynamics International,, Madison, WI, USA P280. LACK OF METABOLIC ACTIVATION, THE PRIMARY REASON RESPONSIBLE FOR NON-TOXICITY OFPLATYNECINETYPE PYRROLIZIDINE ALKALOIDS Jianqing Ruan, The Chinese University of Hong Kong, Hong Kong, Hong Kong P281. FECAL MICROBIOME PROFILING REVEALS ASSOCIATION OF Β-GLUCURONIDASE PRODUCING BACTERIA WITH SUSCEPTIBILITY TO TACRINE-INDUCED HEPATOTOXICITY Lian Yee Yip, National University of Singapore, Singapore, Singapore P282. TOXICITY, GENOTOXICITY AND PROINFLAMMATORY EFFECTS OF AMORPHOUS NANOSILICA IN THE HUMAN INTESTINAL CACO-2 CELL LINE Kevin N. Hogeveen, French Agency for Food, Environmental and Occupational Health and Safety (ANSES), Fougères, France P283. PERSONALIZED DOSING OF DICHLOROACETATE (DCA) BASED ON HAPLOTYPE VARIATIONS IN GLUTATHIONE TRANFERASE ZETA 1 Peter W. Stacpoole, University of Florida, Gainesville, FL, USA P284. EVALUATION OF CRYOPRESERVED HEPARG CELLS AS AN IN VITRO MODEL FOR DRUG-INDUCED BILIARY TOXICITY Rita Ciurlionis, Abbvie, Inc., North Chicago, IL, USA

METABOLIC PROFILING (P292 – P296) P292. HIGH-RESOLUTION MASS SPECTROMETRY FOR RAPID METABOLITE CHARACTERIZATION AND REACTION PHENOTYPING: A CASE STUDY WITH REPAGLINIDE Sylvie Kandel, XenoTech, LLC, Lenexa, KS, USA P293. APPLICATION OF GAS PHASE ION-MOLECULE REACTIONS TO CHARACTERIZE 2-AMINOTHIAZOLE OXIDIZED METABOLITES Minli Zhang, AstraZeneca, Waltham, MA, USA P294. METABOLITE PROFILING ANALYSIS OF CLINICAL SAMPLES - ADDRESSING THE CHALLENGES OF MIST Caroline Anderson, Covance Laboratories Ltd, Harrogate, United Kingdom P295. THE CHANGE OF PLASMA LIPID METABOLISM AT THE ORAL ADMINISTRATION OF ROUSUVASTATIN IN HUMAN Byung Hwa Jung, Korea Institute of Science and Technology, Seoul, South Korea P296. PROFILING AND CHARACTERIZATION OF METABOLITES OF [14C]PONATINIB IN PLASMA, URINE, BILE AND FECES OF RATS AFTER ORAL ADMINISTRATION Yihua Emily Ye, Ariad Pharmaceuticals, Inc, Cambridge, MA, USA

METABOLISM (P297 – P330) P297. AN ACYL GLUCURONIDE STABILITY SCREENING APPROACH IN DRUG DISCOVERY Sara Amberntsson, AstraZeneca R&D, Mölndal, Sweden P298. BMS-820836: STRUCTURAL ELUCIDATION OF HUMAN CIRCULATING N-GLUCURONIDE METABOLITES Van T. Ly, Bristol-Myers Squibb, Princeton, NJ, USA

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Poster Details P299. HUMAN ADME STUDIES: A REVIEW OF OUTCOMES AND THE IMPACT OF STUDY DESIGN VARIABLES Iain Shaw, Quotient Clinical, Nottingham, United Kingdom P300. STABILITY OF GLUTATHIONE ADDUCTS – INFLUENCE ON THE ASSESSMENT OF THE BIOACTIVATION POTENTIAL OF NCES AT EARLY STAGE OF DRUG DEVELOPMENT Joachim Blanz, Novartis Institutes for Biomedical Research, Basel, Switzerland P301. DRIED MICROSOMAL SPOT (DMS): EXPLORING THE FEASIBILITY OF MICRO VOLUME SAMPLING AND DRIED BLOOD SPOT TECHNIQUE FOR IN-VITRO MICROSOMAL METABOLIC STABILITY ASSAYS Gopinadh Bhyrapuneni, Suven Life Sciences Ltd, Hyderabad, India P302. METHODS FOR IMPROVING IN VITRO PREDICTION OF INTRINSIC CLEARANCE UTILISING 3D CELL CULTURE MODELS Phil Butler, Cyprotex, Macclesfield, United Kingdom P303. PHARMACOKINETICS OF ISOLIQUIRITIGENIN AND ITS METABOLITES IN RATS: LOW BIOAVAILABILITY IS PRIMARILY DUE TO THE HEPATIC AND INTESTINAL METABOLISM VIA GLUCURONIDATION Young-Won Chin, Dongguk University, Goyang, South Korea P304. CYP2C8 IS A PREVIOUSLY UNREPORTED IMPORTANT CONTRIBUTOR TO OLANZAPINE OXIDATIVE METABOLISM Porntipa Korprasertthaworn, Flinders University, Adelaide, Australia P305. THE CONTRIBUTION OF HUMAN UDPGLUCURONOSYLTRANSFERASE ENZYMES TO THE GLUCOSIDATION OF MYCOPHENOLIC ACID Nuy Chau, Flinders University, Adelaide, Australia P306. CHARACTERIZATION OF THE BIOTRANSFORMATION OF THE HIV NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR RILPIVIRINE Julie M. Lade, Johns Hopkins University School of Medicine, Baltimore, MD, USA P307. BIOTRANSFORMATION OF BISPHENOL S BY HUMAN AND RAT SUBCELLULAR FRACTIONS :CHARACTERIZATION OF THE CYP450 ISOZYMES INVOLVED Elisabeth F. Perdu, INRA (French National Institute for Agricultural Research), Toulouse, France P308. C-10068: A NOVEL SIGMA AGONIST MORPHINAN WITH A SUPERIOR METABOLISM AND PHARMACOKINETIC PROFILE Vinita Uttamsingh, Concert Pharmaceuticals, Inc., Lexington, MA, USA P309. DEUTERATED ISOTOPOLOGS OF IVACAFTOR HAVE IMPROVED METABOLISM AND PHARMACOKINETIC PROPERTIES Sophia Nguyen, Concert Pharmaceuticals, Inc., Lexington, MA, USA P310. HAPLOTYPE VARIATIONS INFLUENCE HUMAN GSTZ1 GENE EXPRESSION AND THE KINETICS OF THE ANTITUMOR DRUG DICHLOROACETATE (DCA) Margaret O. James, University of Florida, Gainesville, FL, USA P311. IN VIVO RAT METABOLISM OF AN OBESITY DRUG BELORANIB Heasook Kim-Kang, XenoBiotic Laboratories, Inc., Plainsboro, NJ, USA

P312. IN VITRO AND IN VIVO INHIBITION OF N-OXIDATION AND ITS ASSOCIATION WITH HEPATOTOXICITY IN DOG Anthony J. Lee, AbbVie, North Chicago, IL, USA P313. DISPOSITION AND METABOLISM OF [14C]DABRAFENIB, A RAF KINASE INHIBITOR, IN MICE, RATS, DOGS AND HUMANS Lauren E. Richards-Peterson, GlaxoSmithKline, King of Prussia, PA, USA P314. METABOLISM AND DISPOSITION OF [14C]VELUSETRAG, A NOVEL AND HIGHLY SELECTIVE 5HT4 RECEPTOR AGONIST, IN HUMANS Jayaprakasam Bolleddula, Theravance, Inc, South San Francisco, CA, USA P315. VALPROIC ACID AND PRIMARY METABOLITES OF VALPROIC ACID ARE NOVEL ACTIVATORS OF AMPACTIVATED PROTEIN KINASE Lindsay B. Avery, Johns Hopkins University School of Medicine, Baltimore, MD, USA P316. METABOLIC STABILITY ANALYSIS: NOVEL METHOD FOR CORRECTION OF MICROSOMAL BINDING Hinnerk Boriss, Sovicell GmbH, Leipzig, Germany P317. A CLINICAL MICRODOSE STUDY WITH 14CELACYTARABINE IN HEALTHY MALE SUBJECTS TO GENERATE MASS BALANCE DATA TO SUPPORT REGULATORY SUBMISSION: AN INNOVATIVE MICROTRACER APPLICATION Iain Shaw, Quotient Clinical, Nottingham, United Kingdom P318. IN VITRO DRUG METABOLISM BY HUMAN CARBOXYLESTERASE 1 WITH FOCUS ON ANGIOTENSINCONVERTING ENZYME INHIBITORS Ragnar Thomsen, University of Copenhagen, Copenhagen, Denmark P319. ALDO-KETO REDUCTASE 1C3 INDUCES ANTHRACYCLINE RESISTANCE IN CANCER CELLS BY THE REDUCTION OF DAUNORUBICIN AND IDARUBICIN Jakub Hofman, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Hradec Kralove, Czech Republic P320. THE HEPARG CELL LINE: A VALUABLE CELLULAR MODEL FOR BIOTRANSFORMATION AND METABOLOMIC STUDIES Nicolas J. Cabaton, INRA (French National Institute for Agricultural Research), Toulouse, France P321. CHARACTERIZATION OF THE METABOLISM AND ABSORPTION ON NOVEL SYNTHETIC BIOACTIVE PEPTIDES Chunyuan Zhang, The University of Hong Kong, Hong Kong, Hong Kong P322. BIOTRANSFORMATION FROM PYRROLIZIDINE ALKALOID N-OXIDES TO PYRROLIZIDINE ALKALOIDS IN LIVER AND GASTROINTESTINAL TRACT Mengbi Yang, The Chinese University of Hong Kong, Hong Kong, Hong Kong P323. METABOLISM AND EXCRETION OF [14C]EVOGLIPTIN, A DPP-4 INHIBITOR, IN RATS Kyung-Jin Park, Dong-A ST Research Institute, Kyunggi-do, South Korea P324. COMPARATIVE BIOTRANSFORMATION AND MASSBALANCE OF [14C]BMS-754807, A POTENT AND REVERSIBLE ANTAGONIST OF IGF1R, AFTER ORAL ADMINISTRATION TO RATS, DOGS AND HUMANS Peggy Liu-Kreyche, Bristol-Myers Squibb, Princeton, NJ, USA

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Poster Details P325. METABOLISM OF AND ITS IMPACT ON SYSTEMIC EXPOSURE TO TANSHINOL, A VASOACTIVE COMPOUND FROM SALVIA MILTIORRHIZA ROOTS (DANSHEN), IN RATS Junling Yang, Laboratory for DMPK Research of Herbal Medicines, Shanghai Institute of Meteria Medica, Chinese Academy of Sciences, Shanghai, China P326. METABOLIC ACTIVATION OF DAPAGLIFLOZIN AND CANAGLIFLOZIN IN VITRO IN LIVER MICROSOMES AND HEPATOCYTES Thuy Tran, Amgen, Inc, South San Francisco, CA, USA P327. ONTOGENY OF HEPATIC ENERGY METABOLISM GENES IN MICE Helen J. Renaud, University of Kansas Medical Center, Kansas City, KS, USA P328. STRUCTURE-ACTIVITY RELATIONSHIPS OF A SERIES OF 17 PARABENS FOR HISTAMINE RELEASE IN RAT PERITONEAL MAST CELLS, SKIN ALLERGIC REACTION IN GUINEA PIGS, AND HYDROLYTIC ACTIVITY IN RAT AND GUINEA PIG SKIN Naoto Uramaru, Nihon Pharmaceutical University, Saitama, Japan P329. INHIBITORY EFFECT OF HIGH FAT DIET-INDUCED NON-ALCOHOLIC STEATOHEPATITIS WITH FIBROSIS BY PLATYCODON GRANDIFLORUM ROOT-DERIVED SAPONIN IN RATS Jae Ho Choi, Chungnam National University, Daejeon, South Korea P330. INVESTIGATION OF GLUCURONIDE AND SULFATE METABOLITES FORMATION AFTER ORAL ADMINISTRATION OF PARACETAMOL IN HEALTHY HONG KONG CHINESE SUBJECTS Siu kwan Wo, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong

P337. THE ROLE OF ESTERASES IN METABOLISM OF PONATINIB Caroline Woodward, ARIAD PHARMACEUTICALS, Cambridge, MA, USA P338. ENHANCEMENT OF PARAOXONASE 1 (PON1) DETOXICATION ACTIVITY TOWARD NERVE AGENT SURROGATES BY PHENOXYALKYL PYRIDINIUM OXIMES Janice E. Chambers, Mississippi State Univ, Mississippi State, MS, USA

NON-P450 PHASE I ENZYMES (P331 – P338)

PHARMACOGENETICS/PHARMACOEPIGENETICS (P344 – P365)

OXIDATIVE STRESS (P339 – P343) P339. N-HYDROXYLATION OF 4-AMINOBIPHENYL BY CYP2E1 AND ASSOCIATED OXIDATIVE STRESS MAY INFLUENCE ITS TUMORIGENICITY IN MOUSE LIVER Shuang Wang, University of Toronto, Toronto, ON, Canada P340. DEVELOPMENT OF A NOVEL LUMINESCENT ASSAY FOR MEASURING H2O2 IN CULTURED CELLS James J. Cali, Promega Corporation, Madison, WI, USA P341. IRON PROCHELATOR BSIH PROTECTS CARDIAC CELLS AGAINST CATECHOLAMINE-INDUCED OXIDATIVE INJURY Pavlina Haskova, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Hradec Kralove, Czech Republic P342. DIETARY PROTECTION BY GARLIC EXTRACT AGAINST LEAD INDUCED OXIDATIVE STRESS AND GENETIC BIRTH DEFECTS Oladimeji S. Tugbobo, Federal Polytechnic, Ado-Ekiti, Nigeria P343. COMPARISON OF IRON CHELATOR SIH AND OXIDATIVE STRESS-ACTIVATED PRO-CHELATOR BSIH AGAINST OXIDATIVE STRESS-INDUCED CARDIOMYOCYTE DAMAGE Hana Jansova, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Hradec Kralove, Czech Republic

P331. SELECTION OF HUMAN LIVER S9 AND CYTOSOL FRACTIONS FOR EVALUATING CLEARANCE BY ALDEHYDE OXIDASE (AO): THE IMPACT OF LOW VERSUS HIGH AO ACTIVITY LOTS David B. Buckley, XenoTech, LLC, Lenexa, KS, USA P332. A COMPARISON OF ALDEHYDE OXIDASE ACTIVITY IN CRYOPRESERVED HEPATOCYTES FROM MULTIPLE ANIMAL SPECIES: CD-1 MOUSE, SD RAT, WISTAR RAT, BEAGLE DOG, CYNOMOLGUS MONKEY, RHESUS MONKEY AND MAN Utkarsh Doshi, In Vitro ADMET Laboratories LLC, Columbia, MD, USA P333. EVALUATION OF SPECIES AND TISSUE-DEPENDENT DIFFERENCES OBSERVED IN CARBOXYLESTERASE METABOLISM: APPLICATION TO PRO-DRUG STUDIES Katie Fox, Cyprotex, Macclesfield, United Kingdom P334. CHARACTERIZATION OF MICROSOMAL ALDEHYDE OXIDASE ACTIVITY Ryan A. Dick, MyoKardia, South San Francisco, CA, USA P335. SPECIES DIFFERENCES IN HEPATIC AND INTESTINAL ESTERASE ACTIVITIES BETWEEN HUMAN, RAT, DOG AND MONKEY Haruka Nishimuta, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan P336. CHARACTERIZATION OF ESTERASES INVOLVED IN THE METABOLISM OF PARA-NITROPHENYL ACETATE IN HUMAN PLASMA Shin Takusagawa, Astellas Pharma Inc., Osaka, Japan

P344. CYP2D6 GENE LOCUS CHARACTERIZATION BY NEXT GENERATION SEQUENCE (NGS) ANALYSIS Andrea Gaedigk, Children's Mercy Hospital & Clinics, Kansas City, MO, USA P345. INTERINDIVIDUAL VARIABILITY IN TPMT ENZYME ACTIVITY: TEN YEARS OF EXPERIENCE WITH THIOPURINE PHARMACOGENETICS AND THERAPEUTIC DRUG MONITORING Laurent Chouchana, Université Paris Descartes, Sorbonne Paris Cité, Paris, France P346. A PHARMACOGENOMICS STUDY OF SEVERE TOXICITY IN METASTATIC COLORECTAL CANCER PATIENTS TREATED WITH 5-FLUOROURACIL/IRINOTECAN (FOLFIRI)-BASED REGIMENS: RESULTS OF A PROSPECTIVE STUDY Sylvia Chen, Laval University, Quebec, QC, Canada P347. MRP2/ABCC2 GENETIC VARIABILITY INFLUENCES BREAST CANCER SURVIVAL Isa Cavaco, Karolinska Institutet, Stockholm, Sweden P348. EFFECTS OF UGTS AND DRUG TRANSPORTERS POLYMORPHISMS ON PHARMACOKINETICS OF TELMISARTAN IN KOREAN HEALTHY VOLUNTEERS Jae-Eun Kim, Inje University College of Medicine, Busan, South Korea P349. FREQUENCIES AND METABOLIC ACTIVITIES OF THE CYP2D6 GENOTYPES IN KOREANS So-Young Park, Sungkyunkwan University, Suwon, South Korea

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Poster Details P350. EFFECTS OF CYP3A5 GENETIC POLYMORPHISMS ON THE PHARMACOKINETICS OF CILOSTAZOL AND ITS ACTIVE METABOLITES Se Hyung Kim, Sungkyunkwan University, Suwon, South Korea P351. SIGNIFICANTLY HIGHER EXPOSURE OF ACTIVE MOIETY OF CILOSTAZOL IN CYP2C19PM-CYP3A5 NONEXPRESSOR Jung-Eun Lee, Sungkyunkwan University, Suwon, South Korea P352. ASSOCIATION OF BREAST CANCER WITH CYTOCHROME P450 2C19 GENETICS – RISK AND RESPONSE TO ADJUVANT THERAPY Isa Cavaco, Karolinska Institutet, Stockholm, Sweden P353. CYP2D6*10 ALLELE SIGNIFICANTLY INCREASES THE EXPOSURE OF TOLPERISONE Ji-Yeong Byeon, Sungkyunkwan University, Suwon, South Korea P354. EFFECTS OF CYP2D6-CYP2C19 GENOTYPES ON THE PHARMACOKINETICS OF TOLPERISONE Jung-Eun Lee, Sungkyunkwan University, Suwon, South Korea P355. THE EXPOSURE OF TOLPERISONE WAS SIGNIFICANTLY INCREASED IN CYP2C19 POOR METABOLIZERS Jung-Eun Lee, Sungkyunkwan University, Suwon, South Korea P356. NAT2 GENE POLYMORPHISMS IN MEXICAN MESTIZO POPULATION AND THEIR RELATION TO ANTITUBERCULOSIS THERAPY Raul Salazar-González, UASLP, SLP, Mexico P357. EFFECTS OF CYP2C19 GENETIC POLYMORPHISMS ON THE PHARMACOKINETICS OF CILOSTAZOL AND ITS ACTIVE METABOLITES Mi-Jung Kim, Sungkyunkwan University, Suwon, South Korea P358. NR1I2 7635G>A AND POR 831.35C>T SIGNIFICANTLY INCREASE WARFARIN MAINTENANCE DOSES Li-zi Zhao, Institute of Clinical Pharmacology, Guangzhou, China P359. THE EFFECT OF HYPERLIPIDEMIA ON METFORMIN PHARMACOKINETICS IN RATS Raniah Q. Gabr, University of Alberta, Edmonton, AB, Canada P360. CYP2E1 IN HUMAN LIVER: A GENE-DOSAGE INSENSITIVE GENE Roman Tremmel, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany P361. FUNCTIONAL SIGNIFICANCE OF SNPS ON CYP3A4 EXPRESSION AND ACTIVITY IN CAUCASIAN LIVERS Amarjit S. Chaudhry, St. Jude Children's Research Hospital, Memphis, TN, USA P362. THE INFLUENCE OF OATP1B1 AND BCRP GENOTYPES ON THE LIPID LOWERING EFFECT AFTER ADMINISTRATION OF ROSUVASTATIN IN HYPERLIPIDEMIA PATIENTS Li Young Ahn, Seoul National University College of Medicine and Hospital, Seoul, South Korea P363. ABCB1 C.2677G>T/C.3435C>T HAPLOTYPE INCREASES THE EARLY-PHASE ORAL ABSORPTION OF LOSARTAN Joo-Yeon Lee, Sungkyunkwan University, Suwon, South Korea P364. ASSOCIATION OF MRP2/ABCC2 GENETIC VARIABILITY WITH ARTEMETHER-LUMEFANTRINE TREATMENT EXPOSURE Isa Cavaco, University of Algarve, Faro, Portugal

P365. GENETIC VARIATIONS IN UDPGLUCURONOSYLTRANSFERASE 2B15 IN A KOREAN POPULATION Ho Sook Kim, Inje University College of Medicine, Busan, South Korea

PHARMACOKINETICS AND PHARMACODYNAMICS (P366 – P395) P366. PHARMACOKINETICS, TISSUE DISTRIBUTION AND METABOLISM OF ƑÑ-MANGOSTIN FROM GARCINIA MANGOSTANA IN MICE Young Hee Choi, Dongguk University, Goyang, South Korea P367. SIMPLE REVERSED-PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF THE ANTIRETROVIRAL AGENT EFAVIRENZ FROM HUMAN PLASMA Benjamin U. Ebeshi, Niger Delta University, Bayelsa State, Nigeria P368. PHARMACOKINETICS OF DRONEDARONE IN RAT USING A NEWLY DEVELOPED HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC (HPLC) METHOD Yousef A. Bin Jardan, University of Alberta, Edmonton, AB, Canada P369. CAPILLARY MICROSAMPLING IN RATS AND MICE Astrid Capello, WIL Research, Hertogenbosch, Netherlands P370. PHARMACOKINETICS, TISSUE DISTRIBUTION, METABOLISM AND PROTEIN BINDING OF SAUCHINONE IN MICE BASED ON COMBINED LC-MS/MS AND MICROSAMPLING TECHNIQUES: APPLICATION TO EVALUATE THE ADME OF NATURAL PRODUCT IN MICE Young Hee Choi, Dongguk University, Goyang, South Korea P371. PRECLINICAL EVALUATION OF THE Β ISOFORMSPARING PI3K INHIBITOR GDC-0032 AND PREDICTION OF ITS HUMAN PHARMACOKINETICS Jodie Pang, Genentech Inc., South San Francisco, CA, USA P372. PRECLINICAL PHARMACOKINETICS AND IN VITRO METABOLISM OF BMS-605339, A NOVEL HCV NS3 PROTEASE INHIBITOR Susan Jenkins, Bristol-Myers Squibb Company, Wallingford, CT, USA P373. EXPERIMENTAL APPROACH TO INVESTIGATE LUNG PHARMACOKINETIC OF NCES IN RATS AIMED TO REDUCE THE NUMBER OF EMPLOYED ANIMALS Alessandro Fioni, Chiesi Farmaceutici S.p.A., Parma, Italy P374. PLASMA PROTEIN BINDING MEASUREMENT VIA FAST ASSESSMENT OF EQUILIBRIUM BINDING CONSTANTS TO SERUM ALBUMIN AND ALPHA1 ACID GLYCOPROTEIN Hinnerk Boriss, Sovicell GmbH, Leipzig, Germany P375. COMPARISON OF PHARMACOKINETICS OF OSELTAMIVIR AND ITS ACTIVE METABOLITES IN CHINESE HEALTHY VOLUNTEERS VERSUS OTHER ETHNIC GROUPS Zhong Zuo, The Chinese University of Hong Kong, Hong Kong, Hong Kong P376. A PHARMACOKINETIC-PHARMACODYNAMIC (PK-PD) MODEL WITH PREDICTIVE BIOMARKER TO SIMULATE COLORECTAL TUMOR GROWTH IN RATS AFTER 5FLUOROURACIL TREATMENT Shinji Kobuchi, Kyoto Pharmaceutical University, Kyoto, Japan

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Poster Details P377. USE OF HIGH RESOLUTION MASS SPECTROMETRY IMAGING (HR-MSI) COMBINED WITH METABOLOMICS STUDY TO EVALUATE DRUG EFFICACY AND IMPACT ONTO BIOLOGICAL ENVIRONMENT Jonathan Stauber, Imabiotech, Loos, France P378. SIMULATED PAKT/AKT BIOMARKER RESPONSE BASED UPON THE OBSERVED CLINICAL EXPOSURES OF PF-04691502, A PI3K/MTOR DUAL INHIBITOR FROM A PHASE 1 CLINICAL STUDY Ravi Rahavendran, Pfizer Global Research and Development, San Diego, CA, USA P379. PHARMACOKINETICS/TOXICOKINETICS OF AN ANTI5T4 ANTIBODY-DRUG CONJUGATE IN MICE, RATS AND MONKEYS Mauricio Leal, Pfizer, Inc., Pearl River, NY, USA P380. NONLINEAR PHARMACOKINETICS: THE ROLE OF CONCENTRATION-DEPENDENT PARTITIONING TO ERYTHROCYTES IN THE RAT Yaping Tu, GlaxoSmithKline, Research Triangle Park, NC, USA P381. PLASMA PHARMACOKINETICS AND DISPOSITION OF SAPONINS IN RATS AFTER INTRAVENOUS ADMINISTRATION OF SHENMAI INJECTION Wei Niu, Laboratory for DMPK Research of Herbal Medicines, Shanghai Institute of Meteria Medica, Chinese Academy of Sciences, Shanghai, China P382. ANTI FREEZE PROTEIN (AFP): PHARMACOKINETIC AND TISSUE DISTRIBUTION STUDIES IN MICE Stuart G. Wood, Quotient Bioresearch Limited, Rushden, United Kingdom P383. ACOTIAMIDE, A NOVEL ORALLY ACTIVE ACETYLCHOLINESTERASE INHIBITOR FOR THE TREATMENT OF FUNCTIONAL DYSPEPSIA, IS SPECIALLY DISTRIBUTED IN STOMACH Yoshihiro Kawabata, Zeria Pharmaceutical Co., Ltd., Saitama, Japan P384. DRUG DISTRIBUTION WITHIN THE GASTROINTESTINAL TRACK - IN VIVO AND MODELING & SIMULATION EFFORTS TO GUIDE PKPD FOR IBD TARGETS Jean-François Lévesque, Vertex Pharmaceutical Canada, Laval, QC, Canada P385. PLASMA PHARMACOKINETICS AND METABOLISM OF LW6, A NOVEL HYPOXIA-INDUCIBLE FACTOR -1A (HIF-1A) INHIBITOR IN MICE Soo Jin Oh, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, South Korea P386. AUTOMATED BLOOD SAMPLING AND TELEMETRY RECORDING IN AWAKE UNRESTRAINED MACAQUES Brad Gien, BASi, West Lafayette, IN, USA P387. APPLICATION OF A NOVEL COMPUTATIONAL METHOD TO ESTIMATE FEASIBLE SOLUTION SPACES FOR DETERMINING MULTIPLE PARAMETERS IN PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL Kazuya Maeda, The University of Tokyo, Tokyo, Japan P388. METABOLISM AND PHARMACOKINETICS OF PICROSIDE±AND II ISOLATED FROM PICRORRHIZA SCROPHULARIIFLORA Changxiao Liu, Tianjin Institute of Pharmaceutical Reserch, Tianjin, China

P389. MIMICKING HUMAN NICOTINIC ACID EXPOSURE IN PRECLINICAL SPECIES Bianca M. Liederer, Genentech Inc., South San Francisco, CA, USA P390. PHARMACOKINETICS OF SINGLE DOSE OF SUBCUTANEOUS PEGYLATED RECOMBINANT HUMAN GRANULOCYTE COLONY STIMULATING FACTOR (PEGRHG-CSF) IN CANCER PATIENTS: COMPARISON WITH DAILY DOSES OF RHG-CSF Yongming Cai, Tianjin Institute of Pharmaceutical Research, Tianjin, China P391. A MODELING FRAMEWORK FOR THE ASSESSMENT OF [(18)F]-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY IN PREDICTING OVERALL SURVIVAL IN NON-SMALL CELL LUNG CANCER Sebastian Frechen, University of Cologne, Cologne, Germany P392. MILK TRANSFER AND TOXICOKINETICS OF VALPROIC ACID IN LACTATING CYNOMOLGUS MONKEYS Jong-Hwa Lee, Korea Institute of Toxicology, Daejeon, South Korea P393. A PHYSIOLOGICALLY-BASED POPULATION PHARMACOKINETIC MODEL FOR SIMVASTATIN AND ITS ACTIVE METABOLITE SIMVASTATIN ACID Aleksandra Galetin, The University of Manchester, Manchester, United Kingdom P394. DRUG-DRUG INTERACTION STUDY TO ASSESS WHETHER A PHARMACOKINETIC BASIS EXISTS FOR PREVIOUSLY REPORTED COGNITIVE DEFICITS WITH A COMBINATION OF 5-FLUOROURACIL AND LOW DOSE METHOTREXATE Vaishnavi Ganti, Temple University, Philadelphia, PA, USA P395. PHYSIOLOGICALLY-BASED PHARMACOKINETIC AND PHARMACODYNAMIC MODEL FOR THE INHIBITION OF ACETYLCHOLINESTERASE BY ACOTIAMIDE, A NOVEL GASTROPROKINETIC AGENT FOR THE TREATMENT OF FUNCTIONAL DYSPEPSIA, IN RAT STOMACH Kazuyoshi Yoshii, Zeria Pharmaceutical Co., Ltd., Saitama, Japan

RECEPTORS/NUCLEAR RECEPTORS (P396 – P400) P396. UNIQUE ROLE OF PXR IN THE HEPATOCYTE PROLIFERATION IN MICE Ryota Shizu, Tohoku University, Sendai, Japan P397. AHR INACTIVATION BY ALPHA-NAPHTHOFLAVONE AND RESVERATROL INHIBITS CELL PROLIFERATION BY INCREASING P53 AND APOPTOSIS LEVELS IN HELA CELLS Guillermo Elizondo, CINVESTEV-IPN, Mexico, Mexico P398. THE EFFECT OF ERK SIGNALING PATHWAY INHIBITION ON PREGNANE X RECEPTOR (PXR)-MEDIATED CYP3A SUB-FAMILY GENES EXPRESSION Tomas Smutny, Charles University in Prague, Hradec Kralove, Czech Republic P399. SELECTION AND CHARACTERIZATION OF HUMAN CELL LINE SUITABLE FOR ASSESSEMENT OF THYROID RECEPTOR ACTIVATION Peter Illes, Faculty of Science Palacky University Olomouc, Olomouc, Czech Republic P400. LXR MEDIATED UP-REGULATION OF ABCA1 AND ABCG1 THROUGH DOXORUBICIN IN CARDIOMYOCYTES Judith V. Monzel, University of Greifswald, Greifswald, Germany

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Poster Details P412. SPECIES COMPARISON OF BCRP (ABCG2) MEDIATED EFFLUX ON PHARMACOKINETICS OF SUBSTRATE DRUGS USING BCRP KNOCK-OUT RATS AND MICE Christoffer Bundgaard, H. Lundbeck A/S, Copenhagen-Valby, Denmark P413. ENHANCEMENT OF NASAL ABSORPTION OF A PROMISING NOVEL TACRINE DIMER HLS-3 BY COADMINISTRATION WITH P-GLYCOPROTEIN INHIBITOR VERAPAMIL Zhong Zuo, The Chinese University of Hong Kong, Hong Kong, Hong Kong P414. CONTRIBUTION OF OATPS TO DRUG ABSORPTION IN HUMAN INTESTINE IS MUCH LESS THAN PREDICTED Hidenori Takada, The University of Western Ontario, London, ON, Canada P415. STUDY ON TRANSCELLULAR TRANSPORT MECHANISMS OF ACETYLBOSWELLIC ACID IN VITRO Duanyun Si, Tianjin Institute of Pharmaceutical Research, Tianjin, China P416. CANCER-TYPE OATP1B3: FURTHER EVIDENCE ON ITS EXISTENCE AND EXPRESSION PROFILES IN HUMAN LUNG AND COLON CANCER TISSUES Yuchen Sun, Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba-Shi, Japan P417. EXPRESSION OF ORGANIC ANION-TRANSPORTING POLYPEPTIDES (OATP) 2A1, 4A1, 5A1 AND 6A1 AS POSSIBLE BIOMARKERS FOR HUMAN OVARIAN CANCER Juliane Riha, University of Vienna, Vienna, Austria P418. SPECIFIC OATP EXPRESSION PATTERN IN PRIMARY SMALL CELL LUNG CANCER (SCLC) CELL LINES: IMPACT ON DIAGNOSIS AND THERAPY Stefan Brenner, University of Vienna, Vienna, Austria P419. DIFFERENTIAL EXPRESSION OF OATPS, MRP1 AND BCRP TRANSPORTERS AS WELL AS STS AND HSD-1 ENZYMES IN HORMONE DEPENDENT AND HORMONE INDEPENDENT HUMAN BREAST CANCER TISSUES Nilasha Banerjee, University of Toronto, Toronto, ON, Canada P420. MRP4 (ABCC4) PROTECTS CELLS FROM ARSENIC THROUGH THE EXPORT OF DIMETHYLARSINIC ACID (DMAV) AND THE DIGLUTATHIONE CONJUGATE OF MONOMETHYLARSONOUS ACID (MMAIII) Elaine M. Leslie, University of Alberta, Edmonton, AB, Canada P421. RAT IN VIVO FETAL-TO-MATERNAL TRANSFER CLEARANCES OF VARIOUS XENOBIOTICS BY UMBILICAL PERFUSION Tomohiro Nishimura, Keio University, Tokyo, Japan P422. SANDWICH CULTURED HEPATOCYTES: UTILITY IN DELINEATING THE HEPATIC DISPOSITION OF NINE DRUGS SELECTED FROM DIFFERENT BDDCS CLASSES Carina Cantrill, Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester, United Kingdom P423. FUNCTIONAL ASSESSMENT OF OATP1B1 AND BCRP POLYMORPHISMS IN AN OATP1B1/BCRP CO-EXPRESSING MODEL Mark Warren, Optivia Biotechnology Inc., Menlo Park, CA, USA P424. SPECIES DIFFERENCES OF CANALICULAR AND SINUSOIDAL EFFLUX OF MYCOPHENOLIC ACID OGLUCURONIDE IN SANDWICH-CULTURED HEPATOCYTES Kazuhiro Tetsuka, Astellas Research Institute of America LLC, Skokie, IL, USA

RISK ASSESSMENT (P401) P401. METABOLISM AND DISPOSITION OF MELENGESTROL ACETATE IN HUMANS EXTRAPOLATED FROM THE PHARMACOKINETICS IN CHIMERIC MICE WITH HUMANIZED LIVER AND PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING Hiroshi Yamazaki, Showa Pharmaceutical Univ., Machida, Japan

siRNA / microRNA (P402) P402. MIR-137 REGULATES THE CONSTITUTIVE ANDROSTANE RECEPTOR (CAR) AND MODULATES DOXORUBICIN SENSITIVITY IN CANCER CELLS Apana Agha L. Takwi, St. Jude Children’s Research Hospital, Memphis, TN, USA

STEM CELL RESEARCH (P403) P403. EFFECT OF P,P-DDE ON PROLIFERATION AND DIFFERENTIATION OF PROMYELOCITIC CELLS HL-60 Nallely A. Torres, Centro de Investigación y Estudios Avanzados del IPN, México City, Mexico

STEREOSELECTIVE METABOLISM (P404 – P406) P404. NOVEL APPROACH TO IDENTIFYING CYP2C9 RESIDUES RESPONSIBLE FOR STEREOSELECTIVE BINDING AND OXIDATION OF COMPOUNDS Grover P. Miller, Univ of Arkansas for Med Sci, Little Rock, AR, USA P405. STEREOSELECTIVE N-OXIDATION OF BI-A BY CYP3A4 AND FMO3 Hongbin Yu, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA P406. USE OF EFAVIRENZ ANALOGS TO PROBE CYP2B6 SUBSTRATE SPECIFICITY Philip M. Cox, Johns Hopkins University School of Medicine, Baltimore, MD, USA

THERAPY (P407 – P409) P407. COMBINED EFFECT OF SILYBUM MARIANUM AND GLYCYRRHIZA GLABRA ON CCL4 INDUCED LIVER INJURY IN RATIS NORVAGICUS Andleeb Shahzadi, Istanbul University, Istanbul, Turkey P408. PREVENTION OF CISPLATIN-INDUCED NEPHROTOXICITY BY DICHLOROACETATE Philip Board, John Curtin School of Medical Research, Canberra, Australia P409. PHARMACOKINETICS OF SORAFENIB CORRELATES WITH ADVERSE EFFECTS UPON DOSAGE REDUCTION OR WITHDRAWAL IN PATIENTS WITH HEPATOCELLULAR CARCINOMA Miki Shimada, Tohoku University Hospital, Sendai, Japan

TRANSPORTERS (P410 – P470) P410. THE DEVELOPMENT OF A UPLC-MS METHOD FOR THE DETECTION OF 17SS-ESTRADIOL AND ITS METABOLITES IN CELL SAMPLES TO EXAMINE METABOLISM-TRANSPORTER INTERACTIONS Joanna H. Sier, University of Surrey, Guildford, United Kingdom P411. DOES A CHANGE IN THE EXPRESSION OF AQUAPORIN-3 IN THE INTESTINAL TRACT AFFECT DRUG ABSORPTION? Nobutomo Ikarashi, Hoshi Univ, Shinagawa-ku, Japan

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Poster Details P425. FUNCTION OF OAT4/SLC22A11 AS A 16A -HYDROXY DEHYDROEPIANDROSTERONE SULFATE TRANSPORTER AND ITS ASSOCIATION WITH PLACENTAL ESTRIOL SYNTHESIS Tomohiro Tawara, Keio University, Minato-ku, Tokyo, Japan P426. MITOXANTRONE EXPOSURE INDUCED EXPRESSION OF ABCG2 THROUGH ESTROGEN RECEPTOR A AT THE PLACENTAL BARRIER Masatoshi Tomi, Keio University, Tokyo, Japan P427. TRANSPLACENTAL PERMEABILITY OF NUCLEOSIDES AND NUCLEOSIDE-ANALOGUE DRUGS EVALUTED BY RAT FETUS UPTAKE INDEX METHOD Yuichiro Sano, Keio University, Tokyo, Japan P428. SYSTEM-DEPENDENT INHIBITION OF BCRP TRANSPORT BY HIGH- AND LOW-PERMEABLE COMPOUNDS IN BI-DIRECTIONAL MDCKII CELLS AND MEMBRANE VESICLES David B. Buckley, XenoTech, LLC, Lenexa, KS, USA P429. STUDY OF TRANSPORT OF ANTIRETROVIRAL DRUGS ZIDOVUDINE AND LAMIVUDINE ACROSS THE RAT TERM PLACENTA Lukas Cerveny, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Hradec Kralove, Czech Republic P430. ABSENCE OF P-GLYCOPROTEIN TRANSPORT IN THE PHARMACOKINETICS AND TOXICITY OF THE HERBICIDE PARAQUAT Erica L. Woodahl, University of Montana, Missoula, MT, USA P431. COMPARISON OF KI AND IC50 VALUES FOR PROTOTYPICAL AND CLINICALLY-RELEVANT PROBE SUBSTRATES OF THE HEPATIC TRANSPORTERS OATP1B1 AND OATP1B3 David B. Buckley, XenoTech, LLC, Lenexa, KS, USA P432. IN VITRO TRANSPORTER ASSESSMENT OF GDC0068, AN ATP-COMPETITIVE AKT INHIBITOR IN PHASE 1B/II CLINICAL TRIALS Yuzhong Deng, Genentech Inc., South San Francisco, CA, USA P433. LEVERAGING HIGH-THROUGHPUT BSEP INHIBITION ASSAYS TO DRIVE DECISION-MAKING AND ENHANCE UNDERSTANDING OF THE CHOLESTATIC POTENTIAL OF NEW CHEMICAL ENTITIES Kathleen W. Mosure, Bristol-Myers Squibb, Wallingford, CT, USA P434. CHARACTERIZATION OF A NOVEL TRANSPORTER MODEL FOR STUDYING DRUG INTERACTION WITH ORGANIC ANION-TRANSPORTING POLYPEPTIDE (OATP) Na Li, Corning Life Sciences, Bedford, MA, USA P435. VALIDATION OF A NOVEL TRANSPORTER MODEL TO STUDY ORGANIC ANION/CATION TRANSPORTERS Na Li, Corning Life Sciences, Bedford, MA, USA P436. IS INHIBITION OF P-GLYCOPROTEIN (P-GP) SUBSTRATE DEPENDENT? Steven W. Louie, Amgen Inc., Thousand Oaks, CA, USA P437. INTERACTIONS OF ENOBOSARM (OSTARINE, GTX024) WITH A PANEL OF HUMAN DRUG TRANSPORTERS Gang Luo, Covance Laboratories Inc., Madison, WI, USA P438. PREDICTION OF RENAL TRANSPORTER-MEDIATED CLINICAL DRUG-DRUG INTERACTIONS Bo Feng, Pfizer Inc., Groton, CT, USA P439. LEVERAGING A PANEL OF HIGH-THROUGHPUT (HT) TRANSPORTER INHIBITION ASSAYS TO DRIVE DECISIONMAKING AND ENHANCE ADMET KNOWLEDGE Lisa L. Elkin, Bristol-Myers Squibb, Wallingford, CT, USA

P440. QUANTITATIVE EVALUATION OF UNBOUND INTRACELLULAR CONCENTRATIONS OF ANIONIC DRUGS IN RAT HEPATOCYTES Tomohisa Nakada, Mitsubishi Tanabe Pharma Corporation, Chiba, Japan P441. QUANTITATIVE FLUORESCENCE IMAGING OF TRANSPORTER-MEDIATED BILIARY EXCRETION OF TAURO-NOR-THCA-24-DBD IN SANDWICH-CULTURED RAT HEPATOCYTES Tom De Bruyn, KU Leuven, Leuven, Belgium P442. TOWARDS A MORE PREDICTIVE MODEL: EFFECT OF TELMISARTAN ON TAUROCHOLATE DISPOSITION IN BCLEAR® CRYOPRESERVED SANDWICH-CULTURED HEPATOCYTES COMPARED TO BSEP-EXPRESSING MEMBRANE VESICLES Tracy L. Marion, Qualyst Transporter Solutions, Durham, NC, USA P443. TRANSPORTER INHIBITION BY HERBAL SUPPLEMENTS – POTENTIAL DRUG-DIETARY SUPPLEMENT INTERACTIONS Mark Warren, Optivia Biotechnology Inc., Menlo Park, CA, USA P444. CHLOROTHIAZIDE AND TERIFLUNOMIDE AS POTENTIAL BCRP PROBES Remi Magnan, Solvo Biotechnology, Budaörs, Hungary P445. VECTORIAL TRANSPORT OF CHLOROTHIAZIDE BY MONOLAYERS MDCKII CELLS DOUBLY TRANSFECTED WITH HUMAN OAT1 AND BCRP OR WITH OAT3 AND BCRP Remi Magnan, Solvo Biotechnology, Budaörs, Hungary P446. CYCLIN-DEPENDENT KINASE INHIBITORS, FLAVOPIRIDOL, PD 0332991 AND ROSCOVITINE, INHIBIT ABCB1 TRANSPORTER IN VITRO AND SYNERGISTICALLY POTENTIATE THE CYTOTOXIC EFFECT OF DAUNORUBICIN IN MDCKII-ABCB1 CELL LINE Daniela Cihalova, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Hradec Kralove, Czech Republic P447. REDUCED PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR REPAGLINIDE: IMPACT OF OATP1B1 GENOTYPE AND SOURCE OF IN VITRO DATA ON THE PREDICTION OF DRUG-DRUG INTERACTION RISK Aleksandra Galetin, Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester, United Kingdom P448. EFFECT OF PREGNANE X RECEPTOR AGONIST ON THE EXPRESSION OF PLASMA MEMBRANE MONOAMINE TRANSPORTER IN MICE Seokuee Kim, Seoul National University College of Medicine and Hospital, Seoul, South Korea P449. ASSESSMENT OF AFFINITY OF ANTIPSYCHOTIC DRUGS FOR P-GLYCOPROTEIN AND THEIR POTENTIAL FOR DRUG-DRUG INTERACTION Kiyoshi Natsui, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan P450. INVESTIGATION OF THE IMPORATANCE OF MULTIDRUG AND TOXIC COMPOUND EXTRUSION (MATE1) IN THE URINARY EXCRETION OF CATIONIC DRUGS IN MOUSE Hiroyuki Kusuhara, the University of Tokyo, Tokyo, Japan

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Poster Details P451. IDENTIFICATION OF THE PRIMARY HUMAN EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1 MRNA ISOFORMS RESULTING FROM ITS ALTERNATIVE PROMOTER USAGE IN THE LIVER Shogo Matsumoto, Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan P452. ROLE OF HYPOXIA-INDUCIBLE FACTOR 1Α IN THE REGULATION OF CANCER-SPECIFIC VARIANT OF ORGANIC ANION TRANSPORTING POLYPEPTIDE 1B3 (CSOATP1B3) IN COLON AND PANCREATIC CANCER Nilay Thakkar, University of Kentucky, Lexington, KY, USA P453. ABCG2 MRNA ISOFORM EXPRESSION AND DNA METHYLATION PROFILE IN THE MOUSE MAMMARY GLAND Alex Wu, Sickkids Research Institute, Toronto, ON, Canada P454. HEPATOBILIARY TRANSPORT OF ARSENIC IN SANDWICH CULTURED HUMAN HEPATOCYTES Barbara A. Roggenbeck, University of Alberta, Edmonton, AB, Canada P455. P-GLYCOPROTEIN IS RESPONSIBLE FOR THE POOR INTESTINAL ABSORPTION AND LOW TOXICITY OF ACONITINE: THE IN VITRO, IN SITU, IN VIVO AND IN SILICO STUDIES Cuiping Yang, Beijing Institute of Pharmacology and Toxicology, Beijing, China P456. INHIBITORY EFFECTS OF HERBAL MONOMERS ON PGLYCOPROTEIN IN VITRO AND IN VIVO Yan Li, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China P457. DEVELOPMENT OF 96-WELL AUTOMATED OATP1B1 UPTAKE RATE ASSAY FOR LIVER TARGETING Bo Feng, Pfizer Inc., Groton, CT, USA P458. DRUG ACCUMULATION IN ALVEOLAR MACROPHAGES: ASSESSMENT OF UPTAKE AND LYSOSOMAL DISTRIBUTION IN VITRO Ayse Ufuk, Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester, United Kingdom P459. EFFECTS OF MORPHINE AND ITS METABOLITES ON THE EXPRESSION OF AQP3 IN THE COLON Risako Kon, Hoshi Univ, Shinagawa-ku, Japan P460. EFFECT OF RENAL IMPAIRMENT ON THE PHARMACOKINETICS OF MORINIDAZOLE: ALTERED UPTAKE TRANSPORTER-MEDIATED RENAL CLEARANCE? Dafang Zhong, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China P461. ACTIVATION OF XANTHINE OXIDASE SUPPRESSES DISULFIDE BOND FORMATION OF BREAST CANCER RESISTANCE PROTEIN IN CACO-2 CELLS Jiro Ogura, Hokkaido University, Sapporo, Japan P462. IN VITRO FUNCTIONAL ANALYSIS OF NOVEL SINGLE NUCLEOTIDE POLYMORPHISMS IN OATP1B1 Peter Z. Yin, Western University, London, ON, Canada P463. STUDY OF TRANSPORT OF TENOFOVIR AND TENOFOVIR DISOPROXIL FUMARATE ACROSS THE RAT TERM PLACENTA Zuzana Neumanova, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Hradec Kralove, Czech Republic P464. DEVELOPMENT OF A HIGH-THROUGHPUT CELLBASED FLUORESCENCE ASSAY TO STUDY REGULATORY AUTHORITY RECOMMENDED SLC TRANSPORTERS Jie Wang, Corning Life Sciences, Bedford, MA, USA

P465. DEVELOPMENT AND VALIDATION OF A NOVEL TRANSPORTER MODEL TO STUDY REGULATORY AUTHORITY RECOMMENDED SLC TRANSPORTERS Jie Wang, Corning Life Sciences, Bedford, MA, USA P466. THRESHOLD CONCENTRATION OF EXCIPIENTS TO KEEP THE CACO-2 CELLS VIABLE FOR PERMEABILITY AND EFFLUX TRANSPORTER ACTIVITY ASSESSMENTS Bei-Ching Chuang, Millennium Pharmaceuticals, Cambridge, MA, USA P467. THE MECHANISM OF BCRP INHIBITION BY CYCLOHEXANONE ANALOGUES OF CURCUMIN Jezrael L. Revalde, The University of Auckland, Auckland, New Zealand P468. IMPACT OF OATP2B1 EXPRESSION ON CELL PROLIFERATION IN ER-POSITIVE BREAST CANCER Jun Matsumoto, International University of Health and Welfare, Tochigi, Japan P469. RESCUE OF MISFOLDED MRP1 MUTANTS INVOLVING THE HIGHLY CONSERVED CHARGED AMINO ACIDS ARG1202 AND GLU1204 BY HETEROLOGOUS EXPRESSION IN INSECT CELLS Chunying Gao, Queen's University, Kingston, ON, Canada P470. THE INVOLVEMENT OF OATP1B-MEDIATED TRANSPORT IN THE OVERALL HEPATIC CLEARANCE OF HIV PROTEASE INHIBITORS IN MAN Pieter Annaert, KU Leuven, Leuven, Belgium

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Industry-Sponsored Symposia Industry-Sponsored Symposia (ISS) are commercially-supported sessions held in conjunction with the 10th International ISSX Meeting. Although not an official part of the meeting, these symposia have been reviewed and the presentations permitted by ISSX.

Monday, September 30, 2013

07:45 – 08:45 | Pier 4/5 Promega Corporation | Booth 304

07:45 – 08:45 | Harbour Ballroom Thermo Scientific | Booth 502

USING MULTI-PARAMETRIC OPTICAL ASSAYS APPLICATIONS OF HRAM AND NEW TOOLS WITH SPECIALIZED CELL-TYPES TO FOR METABOLITE IDENTIFICATION ENHANCE THE BIOLOGICAL RELEVANCE OF Presented by: Tim Stratton, Thermo Fisher EARLY ADMET SCREENING Scientific and Jeff Gilbert, Dow Agro Sciences Presented by: James Cali, Promega Corporation This symposium is intended to educate researchers in the ADME/Tox area about bioluminescence and how it can be applied to macroscopic measurements of biochemical and cell-based phenomena that are of key importance in the area on ADME/Tox.

The identification of metabolites in a complex sample requires the application of both high performance mass spectrometry techniques and advanced processing tools. The use of very high resolving power instrumentation opens up new opportunities for elemental composition determination beyond accurate mass along which requires complementary processing capabilities.

The target audience for this symposium is researchers interested in characterizing potential drug candidates based on the ADME properties of the compounds as well as researchers interested Join Thermo Scientific for an introduction to our in probing the effects of various treatments on in Next Generation of products and data processing software, including the Orbitrap Fusion Tribrid vitro cell-based model systems. mass spectrometer. In addition, real world examples of solving metabolism problems will be The objectives of this symposium are to discussed focusing on accurate mass and high understand the mechanism behind resolution combined with fragmentation bioluminescence and how it is used to predict techniques and advanced data processing. adverse drug effects; learn how outcomes from bioluminescence correlate with conventional methodologies; learn how bioluminescence can be used to stream-line early ADME/Tox work; understand the advantages/disadvantages of using various cell types to study gene induction; learn how specialized cell-types can be used for ADME studies; learn about recent advances in bioluminescent ADME/Tox assays.

Learn about using high resolution and accurate mass techniques for structure identification studies; fine isotopic data and elemental composition; and techniques for metabolite finding in complex samples.

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Industry-Sponsored Symposia Industry-Sponsored Symposia (ISS) are commercially-supported sessions held in conjunction with the 10th International ISSX Meeting.

Tuesday, October 1, 2013

07:45 – 08:45 | Harbour Ballroom Bruker Daltonics | Booth 303

MALDI IMAGING MASS SPECTROMETRY: BRIDGING BIOLOGY AND CHEMISTRY TO ADVANCE DRUG DEVELOPMENT Presented by: M. Reid Groseclose and Stephen Castellino, GlaxoSmithKline Understanding the distribution of a drug and its metabolites is an essential element in the development of safe and efficacious drugs. The major limitation of using radiolabeled compounds for characterizing drug distributions is the inability to differentiate between the parent drug and metabolites. As a result, radiographic methods are limited in their capability to correlate the engagement of drugs or their metabolites with biological targets responsible for a pharmacological response or pathogenesis.

07:45 – 08:45 | Pier 4/5 Corning Incorporated | Booth 203

USING CELL-BASED AND RECOMBINANT MODELS IN DRUG TRANSPORT Presented by: Na Li, Ph.D. and Inese Smukste, Ph.D., Corning Incorporated

Attendees of the Corning Life Sciences breakfast symposia will gain an understanding of current ABC and SLC drug transporter models available, and be presented with a new single-use cryopreserved SLC drug transporter model.

Data will be presented in the context of regulatory guidance recommendations with respect to transporter-mediated drug-drug interactions and the identification of specific transporters involved in drug transport and elimination. IC50 and Km values comparisons to literature and activity data of the new cryopreserved SLC transporters will be Bruker Daltonics will present data that presented. This new SLC transporter system demonstrates the ability of MALDI IMS to link provides a convenient, high performing chemistry and biology and provide examples of mammalian cell model to support current how this is permitting us to closely examine the basis of drug toxicity and pharmacology and refine regulatory recommendations. our understanding of pharmacokinetics and drug transport. Examples in this presentation will include the distribution analysis of multiple drugs and metabolites in liver tissue and the correlation with observed hepatotoxicity, assessment of the PK/PD relationship for a drug and key metabolites in tissues as well as the comparative CNS penetration and metabolism of a compound in different preclinical models.

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Industry-Sponsored Symposia Industry-Sponsored Symposia (ISS) are commercially-supported sessions held in conjunction with the 10th International ISSX Meeting.

Wednesday, October 2, 2013

07:45 – 08:45 | Harbour Ballroom Hepregen Corporation | Booth 211 HEPATOPAC™ MICROPATTERNED CO-CULTURE SYSTEM - AN IMPROVED IN VITRO MODEL FOR METABOLITE IDENTIFICATION AND COMPOUND STABILITY Presented by: Dr. Caroline Lee, Director of Drug Metabolism and Transporter Sciences, QPS

07:45 – 08:45 | Pier 4/5 Bioreclamation IVT | Booth 401 (formerly Celsis In Vitro Technologies)

PREDICTIONS OF IN VIVO HETEROTROPIC ACTIVATION OF CYTOCHROME P450 ENZYMATIC ACTIVITY FROM IN VITRO SYSTEMS Presented by: Anna L. Bloblaum, Bioreclamation IVT

Investigation of metabolite formation in preclinical This seminar will focus on the emerging trend of species is an important step for understanding the heterotropic activation of cytochrome P450 efficacy and safety of candidate drug molecules. enzymatic activity in vivo and its application to Typically, in vitro systems (liver microsomes or drug discovery. monocultured hepatocytes) are used to identify and compare metabolites among human and In February of 2012 the US Food and Drug animal species before selection of preclinical Administration (FDA) released a draft guidance species for pharmacokinetic, toxicological and with recommendations as to approaches to toxicokinetic studies. However, metabolites identify potential clinical drug-drug interactions formed in vitro often do not correlate with in vivo (DDIs) ranging from P450 to drug efflux protein results. Moreover, metabolites that are unique or victim and perpetrator DDIs. Several mechanisms disproportionately higher in humans require were discussed that can contribute to clinically additional safety testing; thus, in vitro systems that relevant DDIs, including competitive inhibition, offer potentially better up-front predictivity relative mechanism-based inactivation, and induction of to human metabolism provide a likely basis for risk drug metabolizing enzymes. However, as was mitigation and improved efficiency in the product most recently pointed out in a timely perspective development process. (Obach, R.S., Clin Pharm & Therap, 2012, 91(3), 385), the importance of heterotropic effects have We will present results evaluating metabolite re-emerged and the drug metabolism and generation and compound stability using HepatoPac™, a novel micropatterned hepatocyte pharmacokinetics community must address these kinetic phenomena as they consider drug co-culture system, which has the capability to support long duration incubations of test articles discovery, clinical safety and new drug without replacement of culture medium. Several applications. compounds were tested using human, rat and monkey HepatoPac™ culture systems. The metabolites were characterized and profiles were compared with profiles of circulating metabolites observed in human, rat, and monkey. The ability of HepatoPac™ systems to generate relevant in vivo metabolites was compared with that of traditional hepatocyte suspension cultures.

This seminar will the use of recombinant systems, microsomal fractions, and cryopreserved hepatocytes to predict in vivo heterotropic activation of cytochrome P450 3A activity in rodents.

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10th International ISSX Meeting Corporate Sponsors ISSX thanks the following corporate sponsors for their contributions to the 10th International ISSX Meeting. Silver Meeting Sponsor

Booth 203

Meeting Sponsors

Booth 601

Booth 204 ISSX Global Level Partner

Booth 410 ISSX Gold Level Partner

ISSX Gold Level Partner

ISSX Bronze Level Partner

ISSX also thanks the Toronto Convention & Visitors Association for their assistance.

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Join fellow attendees for a delicious dinner in a unique venue that presents Canada’s national sport through the world’s largest collection of hockey artifacts and the fun of interactive games. Attendees can take shots at real-time goalies, stop the shots of Gretzky and Messier, call the play-by-play of some of hockey’s greatest goals, get up close and personal with the Stanley Cup in the museum’s vault, and explore the largest collection of hockey memorabilia in the world. This is the premier social event at this meeting and no better place for attendees to catch up with old friends and make new acquaintances. A separate registration fee of $100 applies. Tickets may still be available. Inquire at the ISSX registration counter in the Metropolitan Ballroom Foyer. Attendees can either meet in the hotel lobby at 18:45 or meet at the Hockey Hall of Fame located a short walk from the hotel at 30 Yonge Street.

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Meeting Co-Chairs Tetsuya Terasaki, Tohoku University Eric Johnson, Scripps Research Institute

Meeting Organizing Committee Kan Chiba, Chiba University Frank Gonzalez, National Cancer Institute Natilie A. Hosea, Pfizer, Inc Takashi Izumi, Daiichi Sankyo Co., Ltd. Scott Obach, Pfizer, Inc. Paul Ortiz de Montellano, University of California - San Francisco Hiroshi Suzuki, The University of Tokyo Hospital Peter W. Swaan, University of Maryland Mikihisa Takano, Hiroshima University Ikumi Tamai, Kanazawa University Toshio Teramura, Astellas Pharama Inc. Hiroshi Yamazaki, Showa Pharmaceutical University Xiao-bo Zhong, University of Connecticut

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2014 is just around the corner! Renew your ISSX Membership today: www.issx.org/renew

Submit an Abstract for the 5th Asia Pacific ISSX Meeting

Tianjin, China May 9 – 12, 2014 We encourage all researchers involved in the investigation of drug metabolism, pharmacology, toxicology, molecular biology, and other related disciplines to consider submitting an abstract for a poster presentation.

www.issx.org/5AP/Abstracts 48


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Exhibitor Directory AB SCIEX Booth 202 AB SCIEX pharmaceutical and biopharmaceutical solutions help accelerate drug discovery and development, spanning across metabolite identification, pharmacokinetics, biologics characterization and regulated bioanalysis. The company’s industry-leading LC/MS/MS solutions include the AB SCIEX TripleQuad 6500 system, TripleTOF 5600+ system, and the Eksigent micro LC 200 system, providing high-performance capabilities that push the limits of pharmaceutical science.

Agilux Labs Booth 111 Agilux Laboratories is a Contract Research Organization (CRO) proudly serving pharmaceutical and biotech clients in North America and around the world. Since our founding in 2008 outside Boston MA., our exceptional service and client responsiveness have allowed us to steadily expand the scope of our capabilities and capacities. Our exceptional service and client responsiveness have allowed us to steadily expand the scope of our capabilities and capacities. We are here to provide you with Better Data Faster. Agilux Laboratories Recognized Again by the Life Science Leader CRO Leadership Awards.

AIM Research Company Booth 207 AIM Research Company provides innovative technologies for radioactivity detection and UPLC/HPLC fraction collection. v.ARC™ DynamicFlow radioisotope detector is the most advanced radioisotope detector on the market for UHPLC and HPLC! LCJet™ system is the fastest fraction collector for UPLC/HPLC. ARC Data System is the comprehensive software system for instrument control and data acquisition, please stop-by our booth for solutions.

Alliance Pharma Inc. Booth 309 Alliance Pharma specializes in GLP and non-GLP bioanalytical services and DMPK support for both small and large molecules. We serve preclinical and clinical programs with LC-MS/MS bioanalysis, metabolism, PK, biomarker and agrochemicals analysis for small molecule; immunoassays for PK or immunogenicity studies and biomarker analysis, cell based assays for biologics.

Alturas Analytics Booth 511 Alturas Analytics is a research-intensive contract research organization (CRO) specializing in regulated LC-MS/MS bioanalysis of small and large molecules. Services include Bioanalytical Method Development and Validation, Routine Quantitative Analysis of Preclinical and Clinical Samples, GLP and Non-GLP. Alturas is a leader in antibody drug conjugate and biomarker analysis using LC-MS/MS.

Bioreclamation IVT Booth 401 Bioreclamation IVT is the premier global provider of hepatocytes, microsomes and other cellular products used for in vitro ADME-Tox research to help speed product development for pharmaceutical and biotechnology companies. We manufacture the highest-quality fresh and cryopreserved products with the largest lot sizes to ensure consistent results every time.

Bruker Daltonics Booth 303 Bruker Daltonics is a leading provider of Separation and Mass Spectrometry instruments for the Analytical Sciences. Our innovative and easy-to-use product families (ESI-TOF, Ion Trap, FTMS, MALDI-TOF, GC, GCMS and ICP-MS) provide the highest performance, highest value systems for a wide range of small molecule and protein analysis applications.

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Exhibitor Directory Busan, Korea, 11th International ISSX Meeting Booth 406 The 11th International ISSX Meeting will be held in Busan, a beautiful convention city located on the south coast of Korea. Stop by the booth to learn more about the 11th International ISSX Meeting to convene June 12 – 16, 2016 in Busan and to learn about Korean culture and outstanding sightseeing in Busan, Korea.

Charles River Booth 400 Charles River is a leading provider of comprehensive drug development services to the pharmaceutical and biotechnology industries. Continued investment in state-of-the-art analytical support, laboratory facilities, in vitro services, metabolism and pharmacokinetics capabilities, proactive program management and a proven approach to integrated drug development, ensures successful client partnerships.

CNBE INRS Booth 305 CNBE is a CRO specialized in low cost exploratory non-GLP studies in animals. CNBE offers toxicity/safety, pharmacokinetic and drug efficacy studies (vaccine, infectious disease, inflammation, immunity, allergy, metabolism, dermatology, wound healing, biomarkers, oncology and stem cell safety) in various animals including rodents, rabbits, pigs/minipigs, ferrets, dogs, sheep, poultry, goats and non-human primates. CNBE has BSL-2 and BSL-3 facilities. CNBE is CCAC and AAALAC International accredited.

Corning Life Sciences Booth 203 Corning Incorporated offers integrated solutions to support life sciences and accelerate drug discovery with products and Contract Research Services for the in vitro analysis of xenobiotic metabolism and drug transport. Products include Corning® Gentest™ Hepatocytes, Tissue Fractions, Transporter Systems, Corning Supersomes™ Enzymes, and Corning Gentest Contract Research Services.

Covance, Inc. Booth 307 Covance, with headquarters in Princeton, New Jersey, is one of the world's largest and most comprehensive drug development services companies with annual revenues of approximately $2.2 billion, global operations in more than 30 countries, and more than 11,750 employees worldwide.

Cypex Booth 410

As well as a wide range of high quality recombinant human, dog, mouse, rat and cynomolgus monkey CYPs and other drug metabolising enzymes such as AOX, ALDH and SULTs, Cypex offers a fast turnaround CYP inhibition screening service, contract protein expression and contract metabolite generation services. Cypex’s CYP inhibition service uses fast fluorimetric assays that give additional information as to whether a compound exhibits time dependent CYP inhibition. All of Cypex’s products and services are covered by their ISO9001-2008 accredited quality assurance system. More information at http://www.cypex.co.uk

Cyprotex Booth 206 Cyprotex is an AIM-listed company (CRX) with headquarters in Macclesfield, UK and laboratories in Watertown, MA, USA (Apredica). The combined company is the leader in predictive toxicology and ADME research, offers several proprietary technologies (CellCiphr®, Cloe®PK, gADMETM) and prides itself on custom assay development and fast turnaround times.

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Exhibitor Directory Eicom USA Booth 408

Please visit the Eicom USA booth to find cutting-edge lab equipment to further your xenobiotics research. Products include 96-well plates specialized for metabolic studies, versatile plate seals that prevent problems with autosamplers, and cleverly designed concentrators. Amuza saves you time and money because our products are specialized and more reliable.

Frontage Labs Booth 405 Frontage Laboratories helps biopharmaceutical organizations advance early-phase research and development with full service offerings– including bioanalysis, preclinical and clinical studies, analytical testing, product development and manufacturing support– that span discovery through Phase II studies. Frontage also provides product development, bioequivalence and analytical services to generic pharmaceutical companies to support ANDA submissions.

HepatoChem Booth 505 HepatoChem’s innovative technology enables fast and cost-effective production of milligram-quantity metabolites. Using biomimetic catalysts, we are able to mimic oxidative metabolism, allowing for metabolite synthesis. We also apply this platform to the rapid production of lead drug candidate analogues. In addition to our services, we sell an easy-to-use metabolite kit.

Hepregen Corporation Booth 211 Hepregen offers a range of ADME/Tox services using HepatoPac™, a novel and highly functional microliver platform. HepatoPac’s organized micro-architecture extends the longevity and functionality of primary hepatocytes, which results in more predictive in vivo outcomes than conventional in vitro models.

Huntingdon Life Sciences Booth 611

Huntingdon Life Sciences, an international Contract Research Organisation offers a comprehensive range of development services to pharmaceutical and biopharmaceutical companies around the world. Our world renowned scientific, technical, and regulatory experts have the breadth and depth of experience to ensure you deliver your R&D milestones. We set the highest standards and offer a broad range of practical support, consultancy and problem solving, all of which can be tailored to meet your specific needs.

HµREL Corporation Booth 409 HμREL® Corporation develops advanced liver tissue constructs and microfluidic cell-based assay platforms for preclinical predictive toxicology, drug metabolism and pharmacokinetics. HμREL®’s stable, high-functioning metabolic competency and long endurance, enable novel in vitro experiments, including clearance rates of low-clearing compounds. HμREL® co-cultures, made from primary human, dog, or rat hepatocytes, facilitate multi-species comparisons.

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Exhibitor Directory International Institute for the Advancement of Medicine (IIAM) Booth 500 IIAM is the world-leading provider of non-transplantable, normal and diseased, human organs and tissues for research, education and development. These biomaterials are recovered within 0-60 minutes from cross-clamp and delivered in 12-24 hours to qualified researchers, scientists, healthcare and biotech professionals for medical and scientific advancement. Visit us at www.iiam.org.

Indigo Biosciences, Inc. Booth 506 With INDIGO's nuclear receptor experts at your service, you get results you can be confident in, every time. With our convenient lab-in-a-box assay kits, you can bring the power of INDIGO into your lab to perform quick, simple, and reliable in-house discovery and toxicology screening. If you'd rather put our experts to the test, send us your compounds and we'll screen them in our lab. Either way, when you need fast, accurate results, trust the Nuclear Receptor Experts. KNOW INDIGO INDIGOBiosciences.com

InterVivo Solutions Booth 312 InterVivo Solutions is a preclinical in vivo CRO providing research services using translational animal models for efficacy, pharmacokinetics, safety and toxicology, including bioanalytical and imaging support. InterVivo specializes in CNS diseases and is unique in its offering of translational models and multi-domain services to improve the clinical success of NCEs.

ISSX Booth 606 ISSX is an international association of scientists that promotes the understanding of the interactions of medicines and chemicals with living systems. As the foremost organization representing the interests of researchers and educators in the field of xenobiotics, the Society is engaged in multiple activities to support, promote, and advance the profession on a global scale.

In Vitro ADMET Laboratories, LLC Booth 208

IVAL manufactures Human and Animal Cryopreserved Hepatocytes as well as tissue culture media and collagen coated plates. IVAL is also a Contract Research Organization for in vitro evaluation of desired and adverse drug properties including metabolism, drug-drug interactions, toxicity, and pharmacology. Expertise includes using primary animal and human cells.

Lablogic Systems, Inc. Booth 302 LabLogic Systems, Inc. is a worldwide market leader in the supply of LIMS and chromatography data systems to the pharmaceutical, agrochemical and nuclear/PET industries. We also design, manufacture, sell and service instruments used in the measurement of low-level radioactivity.

Lhasa Limited Booth 503 An educational charity and active research organization with an enviable reputation for collaborative work within a broad range of industry sectors; Lhasa Limited is a developer of expert knowledge based prediction software and chemical databases.

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Exhibitor Directory Life Technologies Booth 306 Life Technologies Corporation (NASDAQ: LIFE) is a global biotechnology company dedicated to moving science forward to improve life in meaningful ways for everyone. Our premier brands are the most cited, most trusted in the life sciences industry: Invitrogen™, Applied Biosystems®, Gibco®, Molecular Probes®, Novex®, TaqMan®, Ambion®, and Ion Torrent™.

MicroConstants Booth 510 MicroConstants is a GLP-compliant CRO providing DMPK and bioanalytical services to support your discovery, preclinical, and clinical drug development programs. We perform industry-standard in vitro DMPK/ADME assays, custom drug metabolism research, and IND-enabling studies to assess drug-drug interaction potential, metabolic stability, metabolite profiling, and protein binding. Learn more at microconstants.com/dmpk.

MPI Research Booth 612 MPI Research is a preclinical and early clinical CRO that provides discovery, surgery, safety evaluation, bioanalytical, and analytical services. We exceed expectations through consistency and quality, with a commitment to communication and innovation, delivering benefits throughout all phases of development. Learn how we can go beyond for you at www.mpiresearch.com.

Nexcelom Bioscience Booth 308 Nexcelom’s Cellometer line of simple-to-use cell counters automate manual cell counting procedures by obtaining accurate counts, viability, and cell sizes in less than 30 seconds & only 20uL of sample. Fluorescence detection capabilities enable fast & simple determination of GFP transfection rates, PI-viability, & direct counting of WBCs without lysing.

Optibrium Booth 200 Our StarDrop™ software helps guide decisions to select and design high quality compounds with a good balance of properties. StarDrop combines predictive ADME, toxicity and P450 metabolism models and automatic QSAR model building with unique approaches including the Glowing Molecule™ and Probabilistic Scoring to intuitively integrate predicted and experimental data.

Optivia Biotechnology, Inc. Booth 508 Optivia Biotechnology, Inc. is an in vitro transporter assay service provider located in the San Francisco Bay Area in Menlo Park, CA. The Optivia team includes industry veterans with extensive experience in transporters, DMPK/ADME, drug discovery, drug development and regulatory submissions. www.optiviabio.com.

PhoenixBio Co., Ltd. Booth 311 PhoenixBio Co., Ltd. is a company producing the PXB-Mouse® model, a tool for drug discovery and development with a humanized liver up to 95% replaced by human hepatocytes. We provide high quality pre-clinical contract study services in the fields of DMPK/Toxicology and hepatitis virology with this model.

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Exhibitor Directory Promega Corporation Booth 304

Promega is a leader in providing innovative solutions and technical support to the life sciences industry. Promega Corporation’s ADME/Tox product line includes our P450-Glo assays for measuring inhibition/induction of a wide variety of cytochrome P450s as well as our industry leading cell viability reagents for studying cellular toxicity.

Puracyp, Inc. Booth 513

Puracyp is the world’s leader in transcriptional analysis of ADME genes. Our newest panel assays meet all the regulatory challenges associated with induction guidelines. Panel screens to predict induction of human CYP1A2, CYP2B6, CYP3A4 and p-glycoprotein are available. Other panels include transcriptional activation assays from various animal species.

QPS Hepatic Biosciences Booth 209 Founded in 1995, QPS is a GLP/GCP-compliant CRO focused on preclinical and clinical drug discovery and development. QPS Hepatic Biosciences was founded in 2012 by Dr. Edward LeCluyse and Shiloh Barfield, in partnership with the Hamner Institutes, as a center of excellence for QPS, focused on in vitro DMPK, Safety, DDI and DRUG TRANSPORT. Our team is comprised of industry recognized experts.

Qualyst Transporter Solutions, LLC Booth 213 Qualyst Transporter Solutions is the world’s exclusive provider of drug transporter products and contract services utilizing the patented B-CLEAR® technology. The model provides a unique physiologic combination of uptake and efflux transporters with hepatic metabolism. This integrated system addresses questions around clearance, transporter interactions, and cholestasis. Visit us at www.qualyst.com.

Quintiles Booth 103 Through its Bioanalytical and ADME Labs, Quintiles offers 20+ years of scientific leadership with expertise and resources to help pharmaceutical and biotechnology companies identify and address complex issues. We provide a range of in vitro ADME assays and metabolite identification services in support of drug discovery and ADME regulatory filings.

Quotient Bioresearch Booth 210 Quotient Bioresearch is a leading provider of early stage drug development services. Combining the world’s largest radiosynthesis team with a dedicated metabolism facility, we provide seamless integrated ADME services within drug discovery and development. Services include custom radiolabelling (3H, 14C), In Vitro DDI assessments, non-clinical and clinical (Synthesis-to-Clinic) metabolism. www.quotientbioresearch.com

SafeSciMET Booth 507 SafeSciMET provides a new unique and successful private-public European education and training programme in safety sciences for medicines. The programme fulfils needs of the pharmaceutical industry, regulatory authorities, and academia by covering research plus ethical, regulatory and societal aspects in all phases of medicines development. Focus is on holistic, integrative and translational approaches.

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Exhibitor Directory SAGE Labs Booth 407 SAGE Labs specializes in the custom design, development and characterization of unique, next-generation animal research models featuring specific gene deletions, insertions and modifications. We also provide extensive support services for researchers working with animal research models.

Sigma Life Science Booth 411 Sigma® Life Science offers a wide portfolio of innovative technologies to further research in preclinical drug metabolism and safety testing. Using our exclusive CompoZr® Zinc Finger Nuclease technology we are developing novel geneticallymodified cell based assays to increase predictability and improve drug development success.

Simulations Plus, Inc. Booth 101 Modeling and simulation software programs and consulting services - GastroPlus, DDDPlus, ADMET Predictor, MedChem Studio, and MedChem Designer - are used across discovery and development for data mining and drug design, ADME-Tox property prediction, simulation of in vitro dissolution experiments, and prediction of absorption/PBPK/PD/DDI for humans and animals through various administration routes.

SOLVO BIOTECHNOLOGY Booth 204 With 14 years experience and 450 customers in 40 countries, SOLVO Biotechnology is the leading provider of transporter services and products. Leveraging our expertise in efflux and uptake transporters, SOLVO generates quality reports for submission to FDA/EMA. From small molecules to protein therapeutics, SOLVO can test all your transporter needs.

Taconic Booth 310 Taconic is a global provider of genetically modified mouse and rat models and services. Whether you require custom genetically engineered, humanized or research-ready models, Taconic's scientists will partner with you to rapidly and efficiently obtain the high quality models you need.

Tandem Labs Booth 601 Tandem Labs provides large- and small-molecule GLP-compliant bioanalytical services for drugs, metabolites, and biomarkers in a variety of matrices for discovery, pre-clinical, and clinical studies. Our objective is to use our technical expertise to help clients reduce their overall time in bringing new medicines to market.

Thermo Scientific (part of Thermo Fisher Scientific) Booth 502 The Thermo Scientific brand represents Thermo Fisher Scientific’s broad range of laboratory solutions for the life sciences industries. Our product offerings include chromatography, mass spectrometry, and spectroscopy products as well as guaranteed support to meet your analytical needs. Whether your analyses are routine, investigative, advanced research or process oriented, we offer comprehensive solutions for your applications. Our instruments and related technologies are used throughout the chemical, pharmaceutical, biopharmaceutical, proteomics, genomics, ADME/DMPK, polymer, petrochemical, environmental, and food as well as in government and university laboratories.

Triangle Research Labs Booth 504 At TRL we isolate primary hepatocytes from both human and animal liver tissue. We provide both fresh and cryopreserved hepatocytes to our researchers. Our quality standards are very high, thus providing our researchers with the best, most predictive models for their studies.

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Exhibitor Directory University of Washington, Drug Interaction Database Program Booth 602 The Metabolism & Transport Drug Interaction Database (www.druginteractioninfo.org) is a web-based research tool for scientists and clinicians working in the field of drug metabolism, transport, and drug interactions. In vitro and in vivo drug interaction studies, organ impairment and pharmacogenetic PK studies from the literature and NDA Reviews are included in the Database.

Waters Corporation Booth 404 Waters Corporation creates business advantages for laboratory-dependent organizations by delivering scientific innovation to enable customers to make significant advancements. Waters helps customers make profound discoveries, optimize laboratory operations, deliver product performance, and ensure regulatory compliance with a connected portfolio of separations and analytical science, laboratory informatics, mass spectrometry, as well as thermal analysis.

XenoBiotic Laboratories, Inc. Booth 402 XenoBiotic Laboratories, Inc. is a leading contract laboratory specializing in non-clinical and clinical ADME, PK/TK, in vitro drug interaction, transporters and metabolism, bioanalytical method development/validation and clinical sample analysis. XBL is FDA and USDA registered and located near Princeton, NJ. XBL-China is located in Nanjing. Both facilities are AAALAC accredited.

XenoTech, LLC Booth 301 XenoTech is a leading provider of in-vitro GLP and non-GLP contract services and products to support drug discovery and preclinical development; providing unparalleled scientific experience and expertise in evaluating drug candidates as substrates, inhibitors and inducers of P450 enzymes and drug transporters. Visit us online at www.xenotechllc.com.

Exhibitor Check-Off Card ISSX meeting attendees each have an Exhibitor Check-Off Card. Attendees who visit with exhibitors and get a minimum of 20 exhibiting company blocks initialed by a corresponding exhibitor representative will be eligible for one of four great prizes: x x x x

Complimentary Meeting Registration to the 19th North American ISSX Meeting/29th JSSX Meeting at the Hilton San Francisco in October 2014 Four nights lodging (including room & tax) at the Hilton San Francisco Hotel during our meeting dates Free membership in ISSX for 2014 $100 Visa Gift Card

Visit our exhibiting companies and ask an exhibitor staff member to initial your check-off card. Only check-off cards with valid exhibitor initials in a minimum of 20 booth space blocks will be considered to be complete and thereby eligible to be entered into our drawing (although we highly encourage you to visit all of our vendors since they support ISSX and help make this meeting possible). Be sure to clearly print your name on your card and deposit it into the drawing bin located immediately inside the Metropolitan Ballroom Exhibit Hall entrance during the exhibit hall session on Wednesday, October 2 by 13:00. The drawing will be held at the ISSX Booth #606 at 14:00 on Wednesday, October 2. Prize recipients are not required to be present except for the gift card prize.

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Metropolitan Ballroom Exhibit Hall

EXHIBITORS

POSTERS

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10th International ISSX Meeting Proceedings